**4. Discussion**

Addition of Straumann® bone ceramic (60:40; BCP) to autogenous bone did not seem to improve the outcome after 6 months healing time compared to the use of pure BCP in an MSFE, as demonstrated by histomorphometric analyses in the five patients included in the present study. Histomorphometric indices show a high variability, which in most cases can be explained individually. For instance, an oblique section of the cortical maxillary sinus wall could explain, to some extent, the variability mentioned. Compared to autogenous bone, for each biomaterial or combination of graft materials in a maxillary sinus floor elevation (MSFE) procedure a significant lower BV/TV was found (reference

value 41% for autogenous bone) [53]. The autogenous bone graft, in the present study was harvested from the maxillary tuberosity, at the same side as the MSFE procedure was performed, implicating no extra or at least far less morbidity for the patient. However, the disadvantages of a second surgical procedure of harvesting a bone graft should also be taken into account. This disadvantage remains in the situation of a mixed graft, consisting of autogenous bone and a bone substitute.

Since the procedures in this study were similar to the procedures in the previously reported studies using pure BCP as a bone substitute in an MFSE procedure [12,32], it was possible to compare the histomorphometric findings. This analysis showed a difference for trabecular thickness (Tb.Th.) and osteoid surface (OS/BS) but not for the other parameters (BV/TV, OV/BV, and N.Oc/BPM). The osteoid surface suggested a gradual decrease over healing time for pure BCP while the 6-months mixed graft group did not fit in this pattern, which suggests a different healing pattern. Surprisingly, the presence of autogenous bone in the graft does not seem to result in a higher bone volume at 6-months healing time. According to Klijn et al. [9], a healing time of 6 months may not show the ultimate favorable effect in bone regeneration procedures.

In this study, no dental implants were lost during the 5-year follow-up. A minimum native bone height of 4 mm was chosen as a prerequisite to ensure primary stability and high survival rates of the dental implants [12,46] after an MSFE procedure with a bone substitute, regardless of the type of graft used. Klijn et al. indicated that the measured bone volumes are higher in the first stage of healing (first 4.5 months) and in the later stages of healing after 9 months, which indicates that our study design of 6 months healing time does not entirely demonstrate the advantage of adding a bone substitute to autogenous bone. It should, however, be stressed that an MSFE procedure using pure autogenous bone provides a higher vital bone volume after 6 months if a block graft is used compared to a particulate graft or a mixed graft of autogenous bone with a bone substitute [9]. This is also confirmed by meta-analyses on histomorphometric outcome of bone substitutes and autogenous bone grafts in various combinations. Altogether, autogenous bone (and if needed a mixture of autogenous bone with BCP) is superior in terms of the amount of the newly formed bone.

The low number of patients (*n* = 5) in this study was considered a limitation since quantitative histomorphometric data may be less reliable. Indeed, the histomorphometric indices do not always show a clear difference between pure BCP and autogenous bone mixed with BCP. However, qualitative assessment, in contrast, demonstrated consistently a different distribution of bone throughout all biopsies. In the 6-months mixed graft group bone matrix was scattered throughout the entire biopsy with a slightly less dense trabecular pattern in the centers of the grafted area, while in the 6-months pure BCP group a concentration of bone formation at the first 3 mm immediately cranially from the former floor of the maxillary sinus and less bone in the center of the graft was seen. This might be beneficial for bone-to-implant contact (BIC).

Dental implants are endosseous implants, which implicates that the implant should be anchored in and surrounded by vital bone for a stable result with a high (and long lasting) survival rate. In that respect the presence of vital bone over a larger area in grafted sites is important for the longevity of the dental implants to be inserted later. In this study, a minimal native bone height of 4 mm was required to achieve a good primary stability after the MSFE procedure. Using 100% autogenous bone in the MSFE procedure could shorten the healing time to 4 months and would result in a better BIC. If no or not enough autogenous bone is available, alternatively a bone substitute could be added in the MSFE procedure to achieve a good BIC. However, longer healing times (6-, 9- or 12 months studies) should be respected. In our previous studies with pure BCP the optimal healing time seemed to be 9 months, based on the BV/TV, Tb.Th. and O.Th. observed [45]. In cases with less than 4 mm native bone height, an autogenous bone graft is preferably used in an MSFE procedure. If the availability of autogenous bone is limited, it may be considered to use a mixture of autogenous bone and bone substitute to achieve on the one hand a larger graft volume and on the other hand a larger bone volume, that approximates the bone volume in case a full autogenous bone graft is used. The newly formed bone in the present mixed graft study was observed throughout the entire biopsy, suggesting a large

BIC after 6 months. However, the consequences of these findings for dental implant survival still have to be unraveled.
