An Open, Prospective, Non-randomized, Controlled, Multicenter Study to Evaluate Clinical Outcome of the ASTRA TECH Implant System, OsseoSpeed™ Implant in Women Over 60 Years of Age With Osteoporosis/Osteopenia
Phase: NA
Conditions: Postmenopausal Osteoporosis, Osteopenia, Jaw, Edentulous, Partially
Sponsor: Dentsply Sirona Implants and Consumables

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Title:  
An open, prospective, non-randomized, controlled, multicenter study 
to evaluate clinical outcome of Astra Tech OsseoSpeed Implant in 
women over 60 years of age with osteoporosis/osteopenia 
 
 
Identifier:   NCT00745121 
 
Document date:  28-Jan-2010 
 

Protocol synopsis YA-OSS-0007 
 
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28-Jan-2010 
 
An open, prospective, non-randomized, controlled, multicenter study to 
evaluate clinical outcome of Astra Tech OsseoSpeed Implant in women over 
60 years of age with osteoporosis/osteopenia 
 
Sponsor: Dentsply Sirona Implants, Aminogatan 1, Box 14, S-432 21 Mölndal, Sweden 
 
 
Background and overall aim 
Osteoporosis is a systemic skeletal disease affecting more than 75 million people in Europe, Japan 
and USA [1]. It is defined as a condition of decreased bone mineral density (BMD) and changes in 
the microarchitecture of the bone tissue. This leads to decreased bone strength and an increased risk 
of fractures, primarily in the hip, spine and wrist. 
The most common form of osteoporosis is called primary osteoporosis and affects mainly elderly 
patients. It is three times more common in women than in men and this can be explained by the 
lower peak bone mass in women as well as by the hormonal changes that occur at the menopause. 
Furthermore, women live longer than men and thus have larger reductions in bone mass. It has been 
estimated that 30% of all postmenopausal women have osteoporosis [2]. 
It is still not clear whether systemic osteoporosis also results in osteoporosis of the jaws and systemic 
osteoporosis was for a long time considered a contraindication for treatment with dental implants. 
This view has changed over the years but there are still many dentists who consider not to treat 
osteoporotic patients with dental implants due to fear of unsuccessful outcomes. 
The overall aim of the study is to compare treatment with dental implants (the Astra Tech 
OsseoSpeed™ implant) in the maxilla of postmenopausal women with and without systemic 
osteoporosis/osteopenia. 
 
 
Study objectives 
Primary objective 
The primary objective is to compare marginal bone level (MBL) alterations following treatment with 
the OsseoSpeed implant in the maxilla of post-menopausal women with and without systemic 
osteoporosis/osteopenia. Marginal bone level alterations will be evaluated by radiological 
assessments and MBL values at prosthetic insertion will be used as baseline. 
 
Secondary objectives 
The secondary objectives of the study are to evaluate (i.e. compare between the groups): 
• 
Implant survival 
• 
Implant stability, by using resonance frequency analysis (RFA) 
• 
Condition of periimplant mucosa by assessment of Bleeding on Probing (BoP), Probing Pocket 
Depth (PPD) and Attachment Level (AL) 
• 
Safety by recording of adverse events (AEs) and adverse device effects (ADEs) 
• 
Patient reported outcomes by the Oral Health Impact Profile (OHIP) 
 
Additional objective 
The additional objective of the study is to evaluate the correlation between BMD in the skeleton 
(hip/spine) with BMD in the maxilla. 

Protocol synopsis YA-OSS-0007 
 
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Study design 
This will be an open, prospective, non-randomized, controlled parallel-group multicenter study to 
document the outcome of treatment with the OsseoSpeed™ implant in the maxilla of 
postmenopausal women with systemic osteoporosis/osteopenia. Two groups will be included in the 
study: Group A (osteoporosis/osteopenia) consisting of postmenopausal women with low BMD 
values (T-score ≤-2) and Group B (control) consisting of postmenopausal women with normal BMD 
values (T-score ≥-1). Each subject will receive 2-8 splinted implants in the maxilla and two-stage 
surgery will be used. 
A total of 104 subjects fulfilling all of the inclusion criteria and none of the exclusion criteria will 
be included. Fifty-two subjects will be included in group A (osteoporosis/osteopenia group) and 
fifty-two in group B (control). Four centers will be involved in the study, each center treating 13 
osteoporotic/osteopenic subjects and 13 control subjects. 
The study will be a five-year follow-up study comprising of 13 visits: 
 
Visit 1 – Screening 
The screening visit will include collection of demographic data as well as clinical and radiographic 
assessments. Subjects fulfilling all inclusion criteria and none of the exclusion criteria after the 
screening visit will be scheduled for BMD measurements in the hip and the spine, using dual energy 
X-ray absorptiometry (DXA). Subjects fulfilling all inclusion criteria for either Group A or Group 
B and none of the exclusion criteria will be scheduled for Visit 2. 
Visit 2 - Pre-surgical planning 
Subjects will undergo a dental quantitative computed tomography (CT) examination in order to 
determine the BMD at the planned implant sites. The treatment plan will be discussed with the 
subject. 
Visit 3 – Surgery I (Implant placement) 
The surgical procedure will be performed under local anesthesia. After a crestal incision, 2-8 
implants will be placed in the maxilla. Cover screws will then be inserted into the implants and the 
mucoperiosteal flaps sutured back for a tight seal. 
Visit 4 - Post-operative check-up 
One week after implant placement the subjects will return for control of the implants and the healing 
process. 
Visit 5 – Surgery II (Abutment placement) 
At 12 weeks after implant placement, a second surgical procedure will be performed. A small 
mucosal incision will be made under local anesthesia, the cover screws will be removed and healing 
abutments will be connected to the implants. 
Visit 6 – Impression 
After 1 week of soft tissue healing, impressions will be taken for fabrication of the screw-retained 
permanent restoration(s). 
Visit 7 – Permanent restoration (PR) 
The screw-retained permanent restoration will be delivered between 4 and 8 weeks after the 
impression visit. 
Visits 8-13 – Follow-up (PR+6 to 60 months) 
The subject will return for follow-up visits at 6, 12, 24, 36, 48 and 60 months after permanent 
restoration. 
 

Protocol synopsis YA-OSS-0007 
 
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28-Jan-2010 
Rationale for study design 
An open study design has been chosen primarily for ethical reasons since the subjects with 
osteoporosis and osteopenia will be followed-up and treated by their GP:s and therefore will be 
informed about their diagnosis. Furthermore, the treating dentists (the Investigators) need to be 
informed about the subjects’ medication etc. to be able to offer proper therapy. However, the primary 
variable of the study, i.e. marginal bone alterations, will be assessed by blinded independent 
radiologists. 
The reason for including both osteoporotic and osteopenic subjects in Group A is the fact that it 
would be difficult to find a sufficient number of subjects with osteoporosis (T-score ≤-2.5) in need 
of 2-8 implants in the maxilla. By choosing a T-score ≤-2 as an inclusion criterion the subjects will 
still have a reduced, and for the study relevant, BMD and the possibilities of recruiting the required 
number of subjects will be markedly increased. 
A control group (Group B) was included to assure a relevant comparison of the results from Group 
A (osteoporosis/osteopenia) with non-osteoporotic women treated in the same way. 
In order not to jeopardize the treatment results for the subjects, in case the systemic 
osteoporosis/osteopenia actually has an effect on the implant treatment success, a two-stage surgery 
protocol was chosen.  
The subjects will be followed-up for 5 years after prosthetic restoration. The largest marginal bone 
alterations are normally seen within the first year after implant placement. By studying the subjects 
for more than 5 years after implant placement, long-term alterations will be revealed and the 
possibility to detect a difference between the groups will increase. 
 
 
Risk/benefit assessment 
In this study subjects with osteoporosis will be treated with dental implants. This patient group has 
previously often been excluded from implant therapy but since previous studies have shown 
successful results in osteoporotic subjects after implant treatment [3-6] we expect good results in 
both study groups. 
The osteoporotic/osteopenic group will presumably consist both of women with known osteoporosis 
and women with previously unknown osteoporosis. The osteoporotic subjects will be treated 
according to routine health care. This means that some of the patients may have been treated with 
bisphosphonates prior to implant treatment. There is recent data available, describing cases of 
osteonecrosis of the jaws after dental surgery in patients concomitantly treated with bisphosphonates 
[7]. This complication seems to be rare and there is not enough data existing to prove a causal link 
between the use of oral bisphosphonates and osteonecrosis of the jaws. However, we can not ignore 
a small but possible risk for subjects on bisphosphonates to develop osteonecrosis of the jaws. In 
order to minimize this risk, we have chosen not to include patients who have been taking oral 
bisphosphonates for 3 years or more. The subjects will also be carefully informed about the risks of 
osteonecrosis of the jaws before entering the study. This is in accordance with a position paper 
published by the American Association of Oral and Maxillofacial Surgeons [8]. In summary, we 
assess the risk of entering the study as low. The benefit of entering, on the other hand, would be for 
a patient to have an unknown osteoporosis diagnosed and treated. The risk benefit analysis therefore 
must be considered as favorable for entering the study. 
N.B. Oral bisphosphonates is not considered a contraindication for implant treatment. 
 
 

Protocol synopsis YA-OSS-0007 
 
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Study population 
Inclusion criteria 
For inclusion in the study subjects must fulfill all of the following criteria: 
 
1. 
Provision of informed consent 
2. 
Postmenopausal women aged 60 years and over 
3. 
In need of 2-8 implants in maxilla 
4. 
A history of edentulism in the area of implant treatment of at least 6 months. 
5. 
A BMD value suitable either for group A or group B: 
Group A (Osteoporosis/osteopenia): BMD at least 2 standard deviations below mean peak 
bone density of young adults for the spine and total hip (T-score≤-2SD). Absolute values 
(g/cm2) will be used. 
Group B (Control): BMD not more than 1 standard deviation below mean peak bone density 
of young adults for the spine and total hip (T-score≥-1SD). Absolute values (g/cm2) will be 
used. 
Exclusion criteria 
Any of the following is regarded as a criterion for exclusion from the study: 
 
1. 
Unlikely to be able to comply with study procedures, as judged by the investigator. 
2. 
Untreated, uncontrolled caries and/or periodontal disease  
3. 
Known or suspected current malignancy 
4. 
History of chemotherapy within 5 years prior to surgery 
5. 
History of radiation in the head and neck region 
6. 
History of other metabolic bone diseases, e.g. Paget’s disease, hyperparathyroidism, fibrous 
dysplasia or osteomalacia 
7. 
A medical history that makes implant insertion unfavorable 
8. 
Need for systemic corticosteroids 
9. 
Previous or current use of intravenous bisphosphonates (esp. zoledronic acid) 
10. Use of oral bisphosphonates for ≥ 3 years 
11. History of bone grafting and/or sinus lift in the planned implant area 
12. Current need for bone grafting and/or sinus lift in the planned implant area 
13. Present alcohol and/or drug abuse 
14. Involvement in the planning and conduct of the study (applies to both Astra Tech AB staff or 
staff at the study site) 
15. Previous enrolment in the present study. 
16. Participation in a clinical study during the last 6 months. 
 

Protocol synopsis YA-OSS-0007 
 
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Study products 
The OsseoSpeed™ implant is a screw-shaped and self-tapping implant with diameters of 3.5S, 4.0S, 
4.5, 5.0 and 5.0S mm. Implants are available in lengths of 8, 9, 11, 13, 15, 17 and 19 mm. 
MicroThreads™ characterize the coronal aspect of the OsseoSpeed™ implant. 
 
The OsseoSpeed™ surface is developed by a TiO2-blasting procedure creating a rough surface, 
which is then modified through a cleaning process in diluted hydrofluoric acid. 
 
 
Statistical methods 
The primary objective is to test the hypothesis that the alteration in MBL from prosthetic 
restoration to the 5-year follow-up visit is equal (i.e. a two-sided hypothesis) in patients in group A 
and in group B. The hypothesis will be tested by means of the Wilcoxon rank sum test. A p-value 
less than 5% at the 5-year follow-up visit will be considered statistically significant. In addition, 
the time to certain degrees of alterations will be estimated by means of Kaplan-Meier plots and the 
hypothesis that the time is equal in group A and B will be tested by means of the log-rank test. 
 
The secondary objectives are to test: 
− 
The hypothesis that the survival rate is equal among implants on patients in group A and B 
by means of the Fisher’s exact test (i.e. implant level). Furthermore, the time to implant loss 
will be estimated by means of Kaplan-Meier plots and the hypothesis that the time is equal in 
group A and B will be tested by means of the log-rank test. 
− 
The hypothesis that the proportion of survived implants is equal in patients in group A and B 
by means of the Wilcoxon rank sum test (i.e. patient level). 
− 
The hypothesis that the condition of peri-implant mucosa is equal in patients in group A and 
B by means of the Wilcoxon rank sum test. 
 
The evaluation of the correlation between skeletal and maxillary BMD will be estimated by means 
of the Spearman’s rank correlation coefficient on patient level. 
 
All safety variables will be summarized by means of descriptive statistics. No hypotheses will be 
tested. 
 
The hypothesis that the OHIP is equal in patients in group A and B will be tested by means of the 
Wilcoxon rank sum test 
 
All hypotheses will be tested at all visits. P-values will be calculated but not called statistically 
significant except for the primary objective at the final visit. 
 
 
 
Study timetable 
Estimated date of first subject enrolled: 
November 2007 
Estimated date of last subject completed: 
October 2016 
 
 

Protocol synopsis YA-OSS-0007 
 
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References 
1. 
WHO Scientific Group. Prevention and management of osteoporosis, in WHO Technical 
Report Series No 921, W. Press, Editor. 2003. 
2. 
Riggs, B.L. Pathogenesis of osteoporosis. Am J Obstet Gynecol, 1987; 156(5): 1342-6. 
3. 
Amorim, M.A., et al. Comparative study of axial and femoral bone mineral density and 
parameters of mandibular bone quality in patients receiving dental implants. Osteoporos Int, 
2006; 17(10): 1494-500. 
4. 
Becker, W., et al. Osteoporosis and implant failure: an exploratory case-control study. J 
Periodontol, 2000; 71(4): 625-31. 
5. 
von Wowern, N. General and oral aspects of osteoporosis: a review. Clin Oral Investig, 2001; 
5(2): 71-82. 
6. 
Dao, T.T., et al. Is osteoporosis a risk factor for osseointegration of dental implants? Int J 
Oral Maxillofac Implants, 1993; 8(2): 137-44. 
7. 
Van den Wyngaert, T., et al. Bisphosphonates and osteonecrosis of the jaw: cause and effect 
or a post hoc fallacy? Ann Oncol, 2006; 17(8): 1197-204. 
8. 
American Association of Oral and Maxillofacial Surgeons. Position Paper on 
Bisphosphonate-Related Osteonecrosis of the Jaws, Approved by the Board of Trustees 
September 25, 2006. 2006.