Journal of Cranio-Maxillo-Facial Surgery (2010) 38, 222e230

� 2009 European Association for Cranio-Maxillo-Facial Surgery

doi:10.1016/j.jcms.2009.07.004, available online at http://www.sciencedirect.com

Clinical, histological and histomorphometric evaluation of the healing ofmandibular ramus bone block grafts for alveolar ridge augmentation beforeimplant placement*

Alessandro ACOCELLA, Oral Surgery Specialist1, Roberto BERTOLAI, Oral and Maxillo-Facial specialist1,

Maurizio COLAFRANCESCHI, Professor of Human Anatomy and Pathology2, Roberto SACCO, Oral Surgery

Programme Resident3

1Department of Maxillo-Facial Surgery, Faculty of Medicine-University of Florence, Italy; 2Department of HumanAnatomy and Pathology, Faculty of Medicine-University of Florence, Italy; 3Department of Odontostomatology, Facultyof Medicine-University of Sassari, Italy

SUMMARY. Background: Localized bone defects in the maxilla are commonly reconstructed with autologousmono-cortical bone blocks prior to the placement of dental implants. This study presents a clinical, histologicaland histomorphometric analysis on the use of mandibular ramus block grafts for ridge augmentation. Materialsand Methods: mono-cortical bone blocks from the mandibular ramus were grafted in 15 patients. The bonegrafts were left to heal for period varying from 3 to 9 months. Afterwards, 30 implants were inserted andbone samples were removed for subsequent histological analysis. Results: All the bone grafts were successfuland resorption was minimal. There were no implant failures. At graft placement, mean lateral augmentation was4.6 ^ 0.73 mm, which, later, at the time of implant insertion, reduced to 4 ^ 0.77 mm. Histological evaluationindicated signs of active remodelling in all specimens. However, the grafted bone contained substantialamounts of non-vital bone (NVB) and generally weak neo-vascularization regardless of the time ofbiopsies. Conclusions: The outcome of the study suggests that the larger part of osteocytes in mono-corticalbone do not survive grafting and neo-vascularization of non-vital grafted bone is difficult because of the slowremodelling process into new vital. � 2009 European Association for Cranio-Maxillo-Facial Surgery

Keywords: bone histology, bone histomorphometry, mandibular ramus, maxillary defects, mono-cortical boneblock graft

INTRODUCTION

Bone defects in the human maxilla are common. Theyare mostly determined by premature loss of teeth dueto periodontal disease or traumas. They usually causereduction of alveolar bone volume, which becomes, inconsequence, inadequate for standard treatments withosseointegrated implants (Nevins and Mellonig, 1994;Oikarinen et al., 2003).

Pathological resorption of the maxillary bone may bethe main cause of both functional and aesthetic dissatis-faction to the patient (Collins and Nunn, 1994).

Moreover, insufficient bone height and width of the al-veolar ridge make the maxillary anatomy particularly un-favourable for the conventional placement of dentalimplants.

In order to create favourable conditions for implantplacement, the bone must undergo augmentation. Nowa-

*The work should be attributed: Department of Maxillo-Facial Sur-

gery, Faculty of Medicine e University of Florence, Italy; Director:

Dr. Roberto Bertolai, address: Largo Palagi,1 Firenze, Italy.

222

days, reconstruction and augmentation of severelyresorbed maxillary alveolar ridges, with the use of differ-ent grafting materials and techniques, represent a predict-able procedure for endoosseous implant placement.(Buser et al., 1995; Oikarinen et al., 2003; Chiapascoet al., 2007).

There have been experimental in vitro and in vivostudies in all kinds of animal models in order to assessthe quality of bone defects filled with different test mate-rials. The majority of these studies evaluated the osteoin-ductive activities in critical size defect models usingradiography or histology (Bosch et al., 1998; Nidoliet al., 1999).

Recently, there has been considerable interest in boneregeneration augmented with stem cells, periosteum-de-rived cells, or osteoinductive proteins to aid the healingof large skeletal defects (Boo et al., 2002; Yamadaet al., 2003; Lendeckel et al., 2004; Sakata et al., 2006).

It has been widely accepted that autologous bone is themost appropriate grafting material. (Listrom and Syming-ton, 1988; Jensen and Sindet-Pedersen, 1991).

The harvesting sites may be intraoral or extraoral: inthe first case, bone can be harvested from retromolar,

Clinical, histological and histomorphometric evaluation of the healing of mandibular ramus bone block grafts 223

ramus or symphysis areas (Jensen and Sindet-Pedersen,1991; Misch, 1997; Widmark et al., 1997; Hunt andJovanovic, 1999) while in the second case, bone can becollected from ilium, calvarium or tibia. (Block andKent, 1997).

Both mandibular body and ramus area represent anideal donor site as they provide adequate, dense bonewith sufficient volume for implant placement and shorthealing times. (Garg et al., 1998).

The advantages of the ascending ramus donor site overthe chin include minimal patient concern for altered fa-cial contour and low levels of post-operative sensory dis-turbances and discomfort.

Although mandibular ramus mono-cortical blockgrafts for alveolar ridge augmentation have been widelyused with great clinical success, it has not been clearlyexplained how they incorporate into the surroundingbone. The general lack of histological evidence on thehealing of mandibular autogenous bone block graftsleaves a great number of unanswered questions aboutthe biological process.

The vitality of osteocytes is believed to be important inthe process of bone remodelling as it seems that thesecells are involved in bone turnover.

This study’s objective was to gain insight into the vi-tality of bone grafts in the human jaw with emphasis onthe survival of osteocytes used as sign of bone vitality.

Our study has been conducted with an integrated mixof tests and, among them, histomorphometry which hasonly been used in a few studies for the evaluation of os-teocyte survival. (Blomqvist et al., 1998).

MATERIALS AND METHODS

Patients

Fifteen patients (7 men and 8 women) of ages rangingfrom 21 to 53 years were considered for the study(Table 1). The selected patients had severe bone defectsin the maxillary alveolar ridge, originating from peri-odontal disease or traumas.

All 15 patients were healthy and had no general con-traindications for bone block graft surgical treatment;only four of them were smokers.

First of all, a clinical and radiographic investigationwas carried out and the treatment fully explained to thepatients. The treatment programme included a first oper-ation for bone augmentation followed by a healing periodvarying from 3 to 9 months (Table 1); finally, a secondsurgical operation was scheduled for biopsy and implantplacement. All patients gave their informed consent todonate the bone tissue removed during implant surgeryfor histological examination.

First surgical step

The bone augmentation was carried out under local an-aesthesia in 14 patients and under general anaesthesiawith rhino-tracheal intubation in only one case. The lat-ter, in fact, was affected by a larger pre-maxilla defect,which was restored with bilateral ascending ramus grafts.

Full-thickness flaps were reflected in order to allowa satisfactory exposure of the recipient site (Figs. 1a, 2a).The remaining crest width was measured with a pair of cal-lipers to the nearest half-millimeter (pre-augmentationwidth) (Table 2).

After administering block anaesthesia to the inferioralveolar nerve, harvesting of bone from ascending ramuswas performed. An obliqueesagittal incision was madedistal to the third molar following the direction of the ra-mus and a vertical releasing incision was placed distallyin the ramus area. After reflection of bucco-lingual flaps,osteotomies were executed with a small fissure bur tooutline the dimensions of the bone block (Figs. 1b, 2b).Careful techniques were performed to make sure penetra-tion was only of the cortical layer and to avoid any in-juries to the alveolar nerve. Once the osteotomy wascompleted, a straight elevator was placed along the sag-ittal cut and the lateral block of bone was green-stickfractured off (Fig. 2c). The recipient site was preparedby scoring or perforating through and through (witha small, straight fissure bur) in order to create bleedingchannels. The block autograft was then fixated to recipi-ent site with 1 or 2 lag-screws (Osteomed, Addison, TX)(Figs. 1c, 2d). Sharp edges of the bone blocks wererounded off (with large diamond burs) and the aug-mented width of the bony crest was measured againwith a pair of callipers (post-augmentation width).Gaps around the block grafts were filled with bone chipsharvested from the donor site (Fig. 2e). Once the graftwas adapted to the site, an incision through the perios-teum at the base of the flap allowed the tissue coverthe graft without tension. The recipient and the donorsite areas were then sutured with vertical mattress sutures(Vicryl 3-0, Ethicon, Johnson & Johnson Roma, Italy)without covering the bone graft with a barrier membrane(Fig. 2f).

Post-operative antibiotic (Zimox, Pfizer, Latina, Italy)and analgesic (Brufen; Abbott SpA, Campoverde (Lt),Italy) therapy was routinely prescribed for 7 days. Patientswere also given chlorhexidine digluconate 0.2% mouth-wash (Curasept; Curaden Health Care Srl, Milano, Italy)for ten days and sutures were removed after 10e12 days.

Second surgical step

After a healing period of from 3 to 9 months, before theimplant insertion, CT examination was performed inorder to plan implant surgery correctly. The flap wasre-opened with an outline similar to that of the first oper-ation (Fig. 1d). Once the flap was elevated, the healedcrest width was measured again with a pair of callipers(re-entry width) (Table 2). Bone block fixation screwswere removed; implant site preparation and insertionwere accomplished according to standard surgical proto-cols. A total of 30 implants were placed (Table 1) andprimary stability was achieved during this step (maxi-mum insertion torque was 35 Ncm).

Biopsy procedure

Biopsy was performed at the same time of implant place-ment including the grafted bone/recipient site interface.

Table 1 e Patient data and results of histomorphometry means

Patient Sex Age No. of implants Healing time (months) Non Vital Bone(histological %)

1 M 28 6 4 60.72 M 34 2 5 34.33 F 32 1 4 73.24 M 53 2 7 52.75 F 37 3 9 38.46 F 22 2 6 42.37 F 52 2 6 68.28 M 43 1 4 73.49 F 49 1 3 65.210 M 21 2 4 62.311 M 38 2 5 69.812 F 49 1 5 80.513 M 32 2 4 56.214 F 30 1 6 42.315 F 42 2 6 46.8

Fig. 1 e Incisions to the recipient site (a); osteotomies of the mandibular ramus for harvesting a mono-cortical block (b); fixation of the graft to themaxillary defect (c); re-entry at 4 months that show no clinical resorption of the graft (d); connection of the implant inserted with a zirconium abutmentand finalization of the case with a zirconium crown (eef).

224 Journal of Cranio-Maxillo-Facial Surgery

Fig. 2 e View of a maxillary narrow ridge after flap elevation (a); bone osteotomies on mandibular buccal shelf (b); the mono-cortical is out-fractured(c); adaptation and fixation of the graft to the maxillary recipient site (d); gaps around the block grafts were filled with bone chips harvested from thedonor site (e); primary flap closure without tension (f).

Table 2 e Analytical description of the amount of bone augmentation obtained and grafts’ resorption

Case Residual RidgeWidth

Lateralaugmentation atbone grafting

Post augmentationwidth

Re-entrywidth

Re-entry lateralaugmentation

Resorption mm Resorption %

1 3.5 mm 5 mm 8.5 mm 8 mm 4.5 mm 0.5 mm 102 2.5 mm 6 mm 8.5 mm 8 mm 5.5 mm 0.5 mm 8.33 3 mm 5 mm 8 mm 7 mm 4 mm 1 mm 204 3 mm 4 mm 7 mm 6.5 mm 3.5 mm 0.5 mm 12.55 3.5 mm 4 mm 7.5 mm 7.5 mm 4 mm 0 mm 06 4 mm 5 mm 9 mm 7.5 mm 3.5 mm 1.5 mm 307 3 mm 5 mm 8 mm 8 mm 5 mm 0 mm 08 3.5 mm 4 mm 7.5 mm 7 mm 3.5 mm 0.5 mm 12.59 3 mm 5 mm 8 mm 7.5 mm 4.5 mm 0.5 mm 1010 2.5 mm 5 mm 7.5 mm 7 mm 4.5 mm 0.5 mm 1011 2 mm 4 mm 6 mm 5.5 mm 3.5 mm 0.5 mm 12.512 3 mm 4 mm 7 mm 6 mm 3 mm 1 mm 2513 4 mm 5 mm 9 mm 8 mm 4 mm 1 mm 2014 3.5 mm 3 mm 6.5 mm 6 mm 2.5 mm 0.5 mm 16.615 3 mm 5 mm 8 mm 7.5 mm 4.5 mm 0.5 mm 10

Clinical, histological and histomorphometric evaluation of the healing of mandibular ramus bone block grafts 225

226 Journal of Cranio-Maxillo-Facial Surgery

A bone specimen measuring approximately 2.5 mm di-ameter and 8e10 mm long was removed with a hollowtrephine burr of 3 mm outer diameter, accompanied bya copious irrigation. The specimen was carefully re-moved from the trephine burr and the part of the biopsycorresponding to the buccal graft’s cortical plate was la-belled by black Indian ink, for better orientation duringhistology examination.

Histology and histomorphometry

All specimens were immediately fixed in 4% formalde-hyde solution in 0.1 M phosphate buffer (pH 7.3) at4 �C for 24 h. They were then rinsed three times with0.1 M phosphate buffer and, finally, stored at 70% etha-nol at 4 �C, until ready to be embedded. All the biopsieswere cold embedded in methylmethacrylate with 20%N-plastoid (resin solution). Nondecalcified, 5-mm thicksections were made along the axis of the biopsy usinga Jung K microtome. All specimens were, then, stainedwith haematoxylin and eosin. A Leica DM RA micro-scope connected to a computer using an electronic stagetable and a Leica DC 200 digital camera were used forhistomorphometrical measurements. Leica QWin� soft-ware (Leica Microsystems Image Solutions, Rijswijk,the Netherlands) was used to process and measure thedigitised images. This software allows a selection of partsof an image by setting a threshold to the colour of thepixels, which can then, be measured. All measurementswere carried out at �200 magnification in order to allowclear distinction between empty and full osteocyte lacu-nae. The sections stained with haematoxylin and eosinwere used for the measurements of total bone volumeand NVB volume. The mineralized bone tissue containingareas of empty osteocyte lacunae was defined as NVB.NVB was expressed as a percentage of the total bonevolume and its measurement was made semi-automati-cally by outlining the area of empty osteocytes lacunae.

Statistical analysis

All data were analysed using SPSS for Windows 12.0. Asimple regression model was applied to the data in orderto examine the correlation between healing time andNVB (Model: NVBi¼ b0 + b1 moni + 3). The data werepresented as means and standard deviations. Significancewas accepted at the p\0.05 level.

RESULTS

Clinical

All grafts integrated successfully, guaranteeing sufficientbone volume area for implant installation. No significantresorption around the head of the fixation screws was evi-dent. Only one patient exhibited a small graft exposure butthe soft tissue dehiscence resolved spontaneously showingno further complications graft infections. Another patient,who underwent a large bilateral graft from the mandibularbody, experienced a transient hypoesthesia of the lowerlip, which recovered completely within three weeks.

Table 2 analyses the analytical data regarding thegrafting together with rise of bone volume at the timeof grafting and implant placement. The mean boneresorption occurring during healing time was calculatedaccording to the measurements of lateral augmentationat bone grafting and after 3e9 months, at implant place-ment. Considering all the sites together, mean lateralaugmentation, at grafting, was 4.6 ^ 0.73 mm which re-duced to a mean of 4 ^ 0.77 mm at implant insertion;this is equivalent to a mean reduction in the lateral aug-mentation of 13.1 ^ 8.9% (min 10%, max 30%) duringhealing (Table 3).

The number of fixtures placed and the timing of inser-tion for each patient are indicated in Table 1. After sixmonths all 30 implants placed were loaded and all fix-tures were successful, according to Albrektsson criteria(Albrektsson et al., 1986) (Fig. 1eef). In the subsequentfollow-up (average 12-month follow-up), no major com-plications were recorded at donor or recipient sites. Softtissue healing was uneventful, while pain and swellingwere comparable to conventional dento-alveolar proce-dures. Wound dehiscence with graft infection and defin-itive neurosensory deficits at the donor site wase notdetected.

HISTOLOGICAL AND HISTOMORPHOMETRICFINDINGS

Histologically, all specimens showed signs of active re-modelling and all tissues were free of inflammatory cells.Contemporarily, all sections contained both vital andNVB tissue, compact osteonic and trabecular bone. Therepresentation of vital and NVB bone varied consider-ably according to each individual. Bone classed as non-vital (with fields of empty osteocyte lacunae) was pre-dominantly lamellar in type (Fig. 3), while the vitalbone was composed of both lamellar and woven bone.The vital and NVB were in contact with each otherand, sometimes, the latter was completely surroundedby vital bone the former first. The margin between the vi-tal and the NVB coincided with an abrupt change in theorientation of the lamellae (Fig. 3).

As vital bone was in tight contact with the NVB (os-teoconductor), the first replaced the second thanks tocreeping substitution process (Fig. 4). Osteoclasts wererarely detected. Vital bone contained osteocytes in the in-ner core of an osteon, surrounded by NVB, suggestingthat this was recolonized by blood vessels (BV) and os-teogenic cells via the Haversian canal (Fig. 3).

Neovasculature was poorly represented in all speci-mens. At the interface between grafted bone and the re-cipient site, some specimens showed varying amountsof fibrous tissue (FT) mixed with new bone formation(Fig. 4). With the histological analysis alone, very littlequalitative differences could be found among biopsiesat different healing times. The volume of vital andNVB of all patients and the time of healing is presentedin Table 1. The relative NVB volume (NVB as % of totalbone volume) varied from 80.5% (in patient no. 12) to34.3% (in patient no. 2) with an overall average of57.75% of total tissue volume.

Table 3 e Mean and standard deviation in mm of lateral bone augmentation measured at the time of bone grafting and surgical re-entry for implantplacement. Mean percentage reduction in lateral augmentation after grafts healing

Lateral augmentation at bone grafting Re-entry lateral augmentation Resorption %

4.6 ^ 0.73 4 ^ 0.77 13.1 ^ 8.19

Fig. 3 e Histology of the external cortical layer of the ascending ramus graft after 4 (a), 5(b), 6(c; d) months. The pictures show the typical compactosteonic structure of the mandibular ramus but with predominantly empty osteocyte lacunae (NVB) at different healing times. Signs of activeremodelling and new growing vessels are not evident; at a higher magnification vital bone containing osteocytes in the inner core of osteons, surroundedlamellar non-vital bone suggesting that non-vital bone was recolonized by BV and osteogenic cells via the Haversian canals (d). o¼ osteocyte,bv¼ blood vessel, NVB¼ non-vital bone; original magnification �100 (a,b) and �200 (c,d); specimens stained with haematoxylin and eosin.

Clinical, histological and histomorphometric evaluation of the healing of mandibular ramus bone block grafts 227

Statistical analysis

The relationship between variables ‘‘NVB’’ (responsevariable) and ‘‘Months’’ (explanatory variable, lengthof time) looked linear (Fig. 5). A straight line was extrap-olated from the data by the least squares method. Theestimated slope b̂ 1 was negative, indicating that theestimated decrease in NVB per month is around 5.2%.The associated R-squared was around 31%, and itsp-value (as well, of course, as the p-value of the waldtest on the slope coefficient) was moderately significant,showing that the linear relation is good enough. Whilemost of the data points were clustered towards the leftside of the plot, there is just one an observation point,which lies far away from the main cluster of the data(Fig. 5). As this point probably has a major impact onthe regression line, another model omitting this observa-tion was tried. These data suggest that the amount ofNVB decreased slowly as time of healing increased;grafted bone resulted completely revascularized andremodelled after 16.2 months (Fig. 5).

DISCUSSION

Preprosthetic reconstructive surgery of the resorbed max-illa has to create sufficient, good quality bone for implantplacement. Several procedures have been proposed toachieve alveolar ridge augmentation in partially edentu-lous patients. (Buser et al., 1995; de Wijs, 1997).

Bone block graft is the preferred method for many typesof augmentation procedures, since it secures both a sourceof osteogenic cells and a rigid structure for mechanicalsupport. In addition, bone block graft conserves its volumebetter than particulate grafting (Lew et al., 1994).

Autologus bone block grafts have a greater flexibility, asthey can be used in all clinical situations (also in cases ofcomplex), while on the other hand, they show a greaterpotential for post-operative morbidity (risk of graft infec-tion and neurologic sequelae related to bone harvestingin intra-oral site). In fact, harvesting of grafts from themandibular region may cause neurological complications,due to the risk of damage to the inferior alveolar nerve.Recently, a sensory deficit in lower lip and mental areas

Fig. 4 e Grafted bone/recipient site interface after 4 (A) and 6 months (B). (a1) After 4 months a substantial amount of FT, little new vital bone; (a2) ata higher magnification new vital (VB) bone surrounded by NVB with empty osteocyte lacunae, way of resorption (creeping substitution). (b1) After 6months: active bone remodelling with presence of larger amount of vital bone; FT is still present and NVB has not been completely resorbed. (b2) Ata higher magnification, a large amount of new vital bone containing osteocytes; original magnification �100 (a1,b1) and �200 (a2,b2); specimensstained with haematoxylin and eosin.

Fig. 5 e Non-vital bone as percentage of total bone volume relative to time.

228 Journal of Cranio-Maxillo-Facial Surgery

Clinical, histological and histomorphometric evaluation of the healing of mandibular ramus bone block grafts 229

of 8.3% in mandibular ramus harvesting was reported,compared with 16% for the chin as the donor site.

Our clinical findings showed that 9 months post-graft-ing is a sufficient period of time for the grafted bone tointegrate successfully with the original maxillary boneand reach the proper stability for an ideal implantplacement. Moreover, in accordance with literature, theresorption rates reported confirmed the excellent volu-metric stability of the bone block grafts harvested fromascending ramus (Braun and Sotereanos, 1984; Mischet al., 1992; Raghoebar et al., 1996; Cordaro et al.,2002; Schwartz-Arad and Levin, 2005).

Histologically, this work shows that the grafted bonecontained extended parts of NVB (with empty osteocytelacunae) at the time of implant placement. In fact, osteo-cytes require a \0.1-mm proximity to nutrient vessels(Ham, 1952) to survive and interruption of the blood sup-ply results in avascular necrosis (Cruess, 1986). In thissense, our findings correspond with that of Ellegaardet al., 1975 who state that with disruption of BVs,many osteocytes are completely entombed by mineral-ised bone and do not survive the relocation.

Therefore, the presence of deficient neovasculature atdifferent healing times suggests that the dense structureof cortical bone represents a physical obstacle the newvessel growth both from the soft and hard tissues.

From a clinical point of view, it seems important towait for NVB to be replaced by vital bone prior to im-plant placement, since vital bone has better mechanicalcharacteristics (Goldberg and Stevenson, 1987). In thisrespect, the rate by which NVB is resorbed by osteoclastactivity followed by new bone formation is an importantfactor for the osseointegration of implants. There is in-creasing evidence that osteocytes are mechanosensitive(Klein-Nulend et al., 1995) and, for this, they play a cru-cial role in adaptive bone remodelling. Osteocytes maybe involved in the recruitment of osteoclasts or in themodulation of their activity by secreting signalling factors,such as nitrogen oxide, prostaglandins (Klein-Nulendet al., 1995), osteoprotegerin, macrophage colony-stimu-lating factor (M-CSF) and receptor activator of nuclearfactor kappa B ligand (RANKL) (Zhao et al., 2002) or fac-tors related to the apoptosis pathway (Bronckers et al.,1996) induced by ischaemia (Kikuyama et al., 2002).These factors communicate with the bone surface and con-trol the activity of bone surface cells such as osteoblasts,osteoclasts and bone lining cells. (Smit and Burger,2002; Zhao et al., 2002; Zerbo et al., 2003).

As the sample of patients considered by this work isnot relevant, this study does not contribute extensivelyto set new guidelines for the clinical management ofthe correct timing of implant placement after grafting.However, the slow revascularization and remodellingprocesses of mandibular bone blocks suggest waiting atleast 4 months after grafts healing before implant inser-tion. (Aalam and Nowzari, 2007; Felice et al., 2009).

CONCLUSIONS

From a clinical point of view, as supported by literature,this procedure appears to be simple, safe and effective for

the treatment of localized alveolar ridge defects in par-tially edentulous patients. Nonetheless, more studies areneeded to explain the internal micro architecturalchanges occurring during the incorporation and remodel-ling processes in order to draw more definitive conclu-sions about the correct timing of implant insertion andloading.

ACKNOWLEDGMENTS

The authors would like to acknowledge Paolo Nardi MD, DDS,

Carlo Catelani MD, DDS, Pasquale Paglianiti, DDS for their

clinical contribution and overall assistance and Miss Ilaria Pas-

quinelli for English review.

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Dr. Roberto SACCOVia Alcide De Gasperi113 Prato (59100)Italy

Tel: +39 349 5858220E-mail: saccoroberto@yahoo.it

Paper received 7 January 2009Accepted 3 July 2009