A Randomized Clinical Trial of a Modular Cementless Acetabular Metal on Poly Component Versus a Monoblock Cementless Titanium Shell With Ceramic on Ceramic Bearing and CORAIL Stem: A Bone Mineral Density Study
Phase: NA
Conditions: Total Hip Arthroplasty
Sponsor: Ottawa Hospital Research Institute

 
 
 
  
 
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PROTOCOL #: 2010-913-01H 
 
NCT #: NCT01558752 
 
 
 
A Randomized Clinical Trial of a Modular Cementless 
Acetabular Metal on Poly Component versus a Monoblock 
Cementless Titanium Shell with Ceramic on Ceramic Bearing 
and CORAIL Stem: A Bone Mineral Density Study 
 
 
 
 
 
 
 
 
 
 
Paul E. Beaulé MD FRCSC 
J. Mark Wilkinson PhD FRCS 
Laurent Dinh MD FRCPC 
 
 
February 7th, 2013 
Version 4.1 
 

 
 
 
  
 
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INTRODUCTION 
Total hip replacement is one of the most successful surgical interventions of the 
21st century. Current implant designs favor cementless fixation of the acetabular and 
femoral components. Although the fixation on the femoral side has shown excellent long-
term results, there are concerns regarding peri-prosthetic bone loss over time secondary 
to bone removal at the time of implantation as well as abnormal loading over time, also 
called stress shielding. These negative changes in the femoral bone remodeling may play 
a role in the risk of peri-prosthetic fracture. In addition, in order to minimize the risk of 
dislocation as well as improve functional range of motion, surgeons are more commonly 
using large diameter femoral heads which often require a monoblock acetabular 
component which, in the vast majority of cases, requires a metal on metal bearing.  More 
recently, a monoblock shell with a ceramic on ceramic bearing has been introduced to 
avoid metal debris while permitting the use of a large diameter femoral head. However, 
because of the rigidity of the acetabular component, initial fixation and stress-shielding 
over the long-term remain concerns. 
On the femoral side, changes in bone density have been observed with losses most 
pronounced during the first two post-operative years after stem type total hip 
replacement1.  Substantial changes can occur early after the operation2 with between 4 
and 9% loss compared to a post-operative baseline in Gruen zones 1 and 7, depending 
upon the stem, by 6 weeks. In addition, these reported percentage losses exclude the 
actual impact of the operation itself which could have a greater impact upon BMD. The 
broaching technique used in the implanting of the CORAIL stem has been suggested to 
preserve bone density as opposed to other femoral stems. 

 
 
 
  
 
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In addition to BMD measurements one can also assess patterns of load transfer to 
the femoral host bone by measuring biochemical markers of bone turnover from the 
serum or urine, thereby giving mechanistic insights into the longitudinal patterns of bone 
remodelling activity after total hip arthroplasty. Markers such as n-telopeptides of type-I 
collagen (NTX) (degradation of type-I collagen during bone resorption) can be used as a 
surrogate marker of osteoclast activity. Osteocalcin (OC) is another marker secreted by 
osteoblasts and used as a marker of bone formation.3   
Objectives and Hypotheses 
The objectives and hypotheses of this study are as follows: 
1) To prospectively evaluate bone mineral density adjacent to the femoral 
component and femoral bone remodeling of two different designs: CORAIL 
impaction broach titanium stem compared to a modular titanium femoral stem 
(Tri-Lock).  We expect the CORAIL femoral stem group to show significantly 
less bone loss on the femoral side as compared to the Tri-Lock group. 
2) To prospectively evaluate bone mineral density adjacent to the acetabular 
component and acetabular bone remodeling of two different designs: a mono-
block titanium acetabular component with ceramic on ceramic bearing (DELTA 
motion) compared to a modular titanium acetabular component with a 
polyethylene insert (Pinnacle). We do not expect to find any differences in BMD 
on the acetabular side. 
3) To determine if the expression of bone turnover markers (i.e., urinary N-
telopeptides of type-I collagen and serum osteocalcin) differs between the 

 
 
 
  
 
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CORAIL and Tri-Lock/Pinnacle implant designs.  We expect to find higher bone 
remodelling activity in the CORAIL group due to better loading. 
4) To evaluate cup and stem fixation using EBRA software to analyse implant 
migration.   No between group differences in stem or cup migration are expected. 
5) To assess pain, physical function, radiographic and clinical outcome, including 
clinical data regarding survival and complication rates (e.g., dislocation, peri-
prosthetic fracture, etc.).  We expect no significant differences between the two 
groups. 
 
MATERIALS AND METHODS 
Study Design 
 
The proposed study is a prospective, randomized controlled trial.  Participants 
will be recruited from the principal investigators’ practices. 
Primary Outcome Measures 
The primary outcome is percent change in BMD (g/cm2) from baseline (10-14 
days post-op) to the two year post-operative interval, as measured radiographically in 
zones 1 and 7.  Analysis of peri-prosthetic BMD will be achieved using 7 Gruen zones of 
the femoral shaft, which have been used in previous studies (see figure): 

 
 
 
  
 
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Analysis of pelvic peri-prosthetic BMD will be achieved using 4 regions of 
interest (ROI).  This 4-ROI model has been previously described4,5.  As described in 
these papers, the authors “aimed to create simple rectangular ROIs which contained only 
areas of predicted bone loss or bone gain.  The medial and lateral borders of the regions 
are created by two vertical lines; one projected along the medial border of the obturator 
foramen, and the other along the lateral border of the femoral prosthesis. The superior 
limit of region 1 was defined by a horizontal line lying 30 pixels superiorly from a 
horizontal line touching the top border of the cup, which defined its lower limit. Region 2 
extended from here to a horizontal line bisecting the centre of the cup, and region 3 
extended from there to the lower border of the cup. Region 4 extended from the line 
marking the lower border of the cup to a further line lying 30 pixels below that” (see 
figure): 
 
 
 
 
 

 
 
 
  
 
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Secondary Outcome Measures  
N-telopeptides of type-I collagen (NTX) will be used as a surrogate marker of 
osteoclast activity.  Urinary NTX will be measured by electro-chemiluminescent 
immunoassay using a Johnson & Johnson Vitros-ECi analyser (Ortho-Clinical 
Diagnostics, High Wycombe, UK), and expressed as a ratio to urinary creatinine. 
Osteocalcin (OC) will be used as a marker of bone formation3. Serum OC will be 
measured by electrochemiluminescent immunoassay using a Roche Cobas e411 analyser 
(Roche Diagnostics Ltd, Burges Hill, UK).3 
Acetabular and femoral component migration, both vertical and horizontal, will 
be measured on serial radiographs using the computer-assisted Ein Bild Röentgen 
Analyse (EBRA) software for cup and stem migration6-8.  A minimum of three 
comparable radiographs are necessary for calculating the migration curves.  Medial 
migration is defined as negative horizontal movement, distal migration as negative 
vertical movement, and total migration is calculated by the theorem of Pythagorus 
expressing the length of the vector. The 95% confidence limit of EBRA is 1 mm.  
Loosening is defined as a rate of > 2 mm of total migration within the first two years after 
operation. 
 
Patient functional outcomes will be assessed using the Modified Harris Hip Score, 
WOMAC (pain, stiffness and function subscales), RAND-36 Item Health Survey and 
UCLA activity scale.  Complications will also be recorded through clinical follow-ups.  
The complications/adverse events which will be collected during the study include the 
following: dislocation, bone fracture (acetabular and femur), thigh pain, groin pain, 
squeaking and re-operations for non-sepsis. 

 
 
 
  
 
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Inclusion Criteria 
Candidates for the study must meet all of the following criteria: 
❖ Patients who are undergoing primary hip surgery for osteo/degenerative arthritis 
(does not include traumatic arthritis, congenital hip dysplasia, or avascular 
necrosis). 
❖ Patients who are skeletally mature, as determined by Risser sign or at least 18 
years of age. 
❖ Patients under 80 years of age. 
❖ Patients for whom there is a reasonable expectation that they will be available for 
each examination scheduled over a two year post-operative follow-up period. 
Exclusion Criteria 
Candidates will be excluded from the study if any of the following conditions apply: 
❖ Patients with previous fusions, acute femoral neck fractures and above knee 
amputations. 
❖ Patients with evidence of active local infection. 
❖ Patients with systemic neurologic illness adversely affecting gait or weight-
bearing at present. 
❖ Patients who have previously undergone an ipsilateral hemi resurfacing, total 
resurfacing, total bipolar, unipolar or total hip replacement device, or any prior 
hip surgery with retained internal fixation. 
❖ Patients who are anticipated to require contralateral hip surgery in the next year. 
❖ Patients with known disorders of bone metabolism, systemic inflammatory 
disorders, and use of drug medications, including oral steroids, HRT and 

 
 
 
  
 
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Tamoxifen in the past year and any past bisphosphonate therapy, antiresorptives 
or anabolics (such as Teriperative(PTH)). 
❖ Patients with a Body Mass Index (BMI) > 35. 
❖ Patients with neuropathic joints. 
❖ Patients with severe documented psychiatric disease.  
❖ Patients requiring structural bone grafts. 
❖ Patients with an ipsilateral girdlestone. 
❖ Patients with sickle cell disease. 
❖ Patients with major acetabular bone stock deficiency. 
Schedule of Events 
 
Pre-operative Patient Assessment and Planning.  The Inclusion Criteria Checklist 
will be completed to verify patient eligibility with regard to the inclusion and exclusion 
criteria.  In addition, the Patient Informed Consent Form must be read, understood and 
signed by the patient prior to surgery.  Good Clinical Practice Guidelines will be 
followed with respect to obtaining the informed consent.  The Modified Harris Hip Score, 
RAND 36-Item Health Survey, WOMAC and UCLA activity scale will be completed. A 
computer generated randomization list will be used to randomly assign each patient to a 
treatment group.  Pre-operative urine and serum samples will be collected after an 
overnight fast.  Patients will be randomized to one of the two treatment groups using a 
web-based randomization service (www.randomization.com). Randomization will occur 
in blocks of 6 to10 patients.  The size of the block will also be randomized. 
Surgical Procedure.  The CORAIL® Hip System is manufactured by DePuy 
Orthopaedics Inc. (Warsaw, IN), and the components of the Tri-Lock + Pinnacle System 

 
 
 
  
 
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are manufactured by DePuy Orthopaedics Inc. (Warsaw, IN). The mono-block acetabular 
component will be the Delta Motion and the modular titanium acetabular component will 
be the Pinnacle/Tri-Lock system with highly cross-link polyethylene insert, manufactured 
by DePuy. The femoral component will be a titanium HA-coated tapered design 
CORAIL stem from Depuy, or a Tri-Lock stem from DePuy. Patients will receive the 
component that they are randomized to.  Operative details will be recorded on the 
appropriate Case Report Form. 
 
Post-operative Clinical Evaluation. Each patient will be evaluated by the 
investigator at their regularly scheduled 10-14 days, 3, 6, 12 and 24 month visits 
following surgery, which includes both clinical and radiographical evaluations. 
Additional safety data beyond two years will be collected (as per standard of practice) but 
safety and effectiveness analyses will be based on two-year data.  
 
Bilateral DEXA bone mineral density tests will be performed at 10-14 days 
following surgery (baseline assessment) and at 6, 12, and 24 months post-operatively. 
Urine and serum samples will be collected at 3, 6,12 and 24 months post-
operatively after an overnight fast.  
 
The range of motion clinical assessment will be completed at each post-operative 
visit except the immediate (10-14 days), when risk of dislocation precludes a 
determination of range of motion.  At the 3, 6, 12 and 24 month post-operative visits, the 
patient will complete the Modified Harris Hip Score, RAND-36 Items Health Survey, 
WOMAC and UCLA activity scale. 
 
Clear AP and lateral radiographs that profile the femoral and acetabular 
components will be obtained at each follow-up visit for migration analysis with EBRA.  

 
 
 
  
 
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Specifically, an AP pelvis and a Lowenstein lateral view that profile the femoral and 
acetabular components are required.  The surgeon will evaluate the radiographs and 
complete the appropriate Case Report Form. 
 
Any of the following complications or adverse events (dislocation, bone fracture 
(acetabular and femur), thigh pain, groin pain, squeaking and re-operations for non-
sepsis) that occur during the study, will be documented by the completion of the 
Complications/Adverse Events Form.  This form will be completed as soon as the 
investigator becomes aware of the complication, whether the patient is within a post-
operative evaluation interval or not.  Complications and adverse events will be reported 
as appropriate to the Research Ethics Board and/or DePuy Orthopaedics Inc..  Patient 
follow-up will continue in accordance with the protocol, i.e., for a two-year post-
operative period at designated intervals.  
Proposed Sample Size and Enrollment Period 
A review of the literature reveals that peri-prosthetic BMD tends to vary 
substantially among normal, healthy individuals, with a standard deviation (SD) that is 
approximately 20% of the mean BMD.  Based on a recommendation from the WHO that 
a loss of at least 1 SD in BMD is required before diagnosing osteopenia, and a loss of 2.5 
SD in BMD constitutes osteoporosis, we believe that a loss of 0.5 SD in BMD – 
equivalent to a 10% loss in BMD – is the minimal clinically important difference (MCID) 
when using this outcome.  This study will be powered to detect the MCID in BMD 
between the two groups being compared.  
No bone mineral density data have been reported for the CORAIL stem on which 
to directly calculate the sample size. Using values based upon data for an uncemented 

 
 
 
  
 
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femoral prosthesis9,10 and assuming a difference of 0.14 g/cm2 (SD=0.23 g/cm2) at 10-14 
days post-operatively for a combined area covering Gruen Zones 1 and 7, 43 participants 
per group are required for 80% power at a 5% significance level. This would translate to 
a 10% difference in percentage change from baseline between groups assuming a 
deterioration of 5% in the CORAIL group. To allow for 15% drop-out over 2 years, this 
was inflated to 102 participants, allowing both short-and medium-term BMD to be 
assessed. 
 
Based on previous literature, we can assume a migration rate of 1.5 mm in the 
first 24-months with a standard deviation of .65.  Using 80% power and an α level of .05, 
40 patients per group are required to detect a difference of .365 mm.  A difference of ½ 
standard deviations is considered clinically significant.  This study is therefore, 
adequately powered to detect a significant difference in component migration. 
 
This prospective randomized trial will take place at the Ottawa Hospital-General 
Campus.  To compensate for the loss of data from five participants due to the change of 
the implant type (Profemur to Tri-Lock) during the early phase of the study, a total of 108 
unilateral hips will be enrolled into the study group with 54 in each treatment arm.  Each 
of the 5 orthopaedic investigators performs approximately 5 primary total hip 
replacement surgeries per month. Approximately 5 of these patients would meet the 
inclusion/exclusion criteria and would agree to participate in the study.  Therefore it 
should take approximately 18-24 months to recruit 108 patients. 
 
STATISTICAL METHODS 
Bone Mineral Density 

 
 
 
  
 
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Independent t-tests will be used to compare percent bone loss between the 
CORAIL and Tri-Lock/Pinnacle groups at the 10-14 days time interval, for both the 
acetabular and femoral components.  Repeated measures ANOVAs will also be used to 
determine if there are any differences between the groups in terms of the pattern of bone 
density loss over the post-operative testing intervals. 
Bone Turnover 
Repeated measures ANOVAs will be used to determine the change in biomarkers 
between the CORAIL and Tri-Lock/Pinnacle implants. 
Functional, Radiographic and Secondary Outcome Measures 
 
 
Independent samples t-tests will be used to compare the secondary outcomes 
(WOMAC, RAND-36, UCLA Activity Scale, Modified Harris Hip) from the CORAIL 
sample to the Tri-Lock/Pinnacle group.  Further, paired t-tests will be used to evaluate 
whether there are changes in the functional outcome scores as the subjects are followed 
prospectively.  Specifically, comparisons to baseline values will be made at 6, 12, and 24 
months of follow-up.  The EBRA software will be used to analyze implant migration. 
Plain radiographic measurements will be done of femoral offset and leg lengths. 
Survival and Complication Rates 
 
 
The frequency distribution of different types of complications will be tabulated.  
Overall rates of complication for the study subjects will be evaluated using Kaplan Meier 
methodology.  The rates of complication in the Tri-Lock/Pinnacle group will be 
compared to the complication rates for the CORAIL group.  Ninety-five percent 
confidence intervals will be constructed for the cumulative survival rate at specific 
benchmark time periods including one year and two years. The primary comparison will 

 
 
 
  
 
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exclude hips lost-to-follow-up because of death.  Other withdrawals completely unrelated 
to safety such as those due to extreme trauma (e.g., car accidents) will also be excluded.  
In addition, the two-year survival computed from the Kaplan Meier survival curve will be 
presented in order to provide an intent-to-treat estimate.  This value will include data 
from all enrolled hips up to the point of censorship for any reason.  Separate Kaplan 
Meier survival curves will be drawn for males and females and for patients younger and 
older than the median age in the sample to determine if patient gender and age at time of 
implant are related to survival over time.  Statistical significance for gender and age 
effects will be assessed using logrank statistics.  The objective of this analysis will be to 
see if any specific subgroup is at particular risk for failure.  This analysis will use data 
from all enrolled subjects up to the point of censorship. 
 
 

 
 
 
  
 
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