4 SUBJECTS AND METHODS
4.1 Subjects and study design
There were three different populations in the present study. The first three sub-groups consisted of patients in the “Knee DXA Study” and the fourth subgroup of patients in the “Verity Study” at Kuopio University Hospital (KUH). The study protocols were approved by the local ethics committee (decision numbers 71/1997 and 54/2011, respectively). All patients gave written informed consent.
All patients in the Knee DXA Study (subgroups described in original publica-tions I-III, n = 112) underwent cemented TKA for OA. The patella was resurfaced in all patients. 121 TKAs with all 3 components cemented using standard techniques were conducted. The implants used were Duracon (Howmedica Inc., Rutherford, New Jersey, USA n = 67), Nexgen (Zimmer, Warsaw, Indiana, USA, n = 36), AMK (DePuy, Warsaw, Indiana, USA, n = 14) and AGC (Biomet Ltd, Bridgend, United Kingdom n = 4). All patients were operated upon by experienced orthopedic sur-geons. A tourniquet was used for all patients except two. Antibiotic prophylaxis was provided with cefuroxime to except two patients, who received vancomycin.
Full weight-bearing was allowed immediately after the operation in all patients.
Continuous passive motion (CPM) devices were used for total of 40 patients. All patients received mechanical (medical compression stockings) and pharmacological thromboprophylaxis with warfarin (n = 3) or low molecular weight heparin (dalte-parin n = 3, enoxaparin for the rest of the patients). The American Knee Society score (AKS) was used to clinically evaluate the knee status and function during daily activities preoperatively and at each follow-up visit—3 months and 1, 2, 4, and 7 years postoperatively. The patients were free of any diseases and medications known to influence bone mineral metabolism, which was also confirmed at every follow-up visit and appointment for BMD measurement throughout the follow-up period. All women had reached their physiological menopause. A long standing radiograph was taken both preoperatively and at each follow-up visit, to measure the tibiofemoral angle.
In the first subgroup, 86 patients were recruited from the waiting list of the or-thopedic department at Kuopio University Hospital between May 1997 and Febru-ary 2001. The study material consisted of 91 knees with primFebru-ary and 3 knees with posttraumatic OA (previous meniscectomy or anterior cruciate ligament rupture).
Furthermore, in 1 knee, there was an aseptic bone necrosis of the lateral femoral condyle. Knees with previous fractures were excluded. TKAs with all 3 components
3 AIMS OF THE STUDY
The aims of the present study were:
I. To explore the medium-term BMD changes in tibial periprosthetic bone after TKA, focusing on the effect of mechanical axis correction to de-crease the periprosthetic BMD of the preoperatively more loaded tibial condyle.
II. To investigate if one-year oral alendronate therapy supplemented with calcium could lead to improved BMD compared to treatment with cal-cium supplementation alone in a group of cemented primary TKA pa-tients in a medium-term follow-up.
III. To investigate the medium-term BMD changes of the contra- and ipsi-lateral hips and the contraipsi-lateral knee after TKA. The hypothesis was that the operation can preserve or even increase the BMD of the neigh-boring joint bones.
IV. To determine the possibilities of CBCT to examine the knee status after total knee arthroplasty and validate the technique in symptomatic TKA. To evaluate the rotation and loosening of the components as well as the osteolysis and quality of the periprosthetic bone.
4 SUBJECTS AND METHODS
The following section gives a brief introduction of the subjects and methods, which are presented in detail in the original publications I-IV.
4.1 SUBJECTS AND STUDY DESIGN
There were three different populations in the present study. The first three sub-groups consisted of patients in the “Knee DXA Study” and the fourth subgroup of patients in the “Verity Study” at Kuopio University Hospital (KUH). The study protocols were approved by the local ethics committee (decision numbers 71/1997 and 54/2011, respectively). All patients gave written informed consent.
All patients in the Knee DXA Study (subgroups described in original publica-tions I-III, n = 112) underwent cemented TKA for OA. The patella was resurfaced in all patients. 121 TKAs with all 3 components cemented using standard techniques were conducted. The implants used were Duracon (Howmedica Inc., Rutherford, New Jersey, USA n = 67), Nexgen (Zimmer, Warsaw, Indiana, USA, n = 36), AMK (DePuy, Warsaw, Indiana, USA, n = 14) and AGC (Biomet Ltd, Bridgend, United Kingdom n = 4). All patients were operated upon by experienced orthopedic sur-geons. A tourniquet was used for all patients except two. Antibiotic prophylaxis was provided with cefuroxime to except two patients, who received vancomycin.
Full weight-bearing was allowed immediately after the operation in all patients.
Continuous passive motion (CPM) devices were used for total of 40 patients. All patients received mechanical (medical compression stockings) and pharmacological thromboprophylaxis with warfarin (n = 3) or low molecular weight heparin (dalte-parin n = 3, enoxaparin for the rest of the patients). The American Knee Society score (AKS) was used to clinically evaluate the knee status and function during daily activities preoperatively and at each follow-up visit—3 months and 1, 2, 4, and 7 years postoperatively. The patients were free of any diseases and medications known to influence bone mineral metabolism, which was also confirmed at every follow-up visit and appointment for BMD measurement throughout the follow-up period. All women had reached their physiological menopause. A long standing radiograph was taken both preoperatively and at each follow-up visit, to measure the tibiofemoral angle.
In the first subgroup, 86 patients were recruited from the waiting list of the or-thopedic department at Kuopio University Hospital between May 1997 and Febru-ary 2001. The study material consisted of 91 knees with primFebru-ary and 3 knees with posttraumatic OA (previous meniscectomy or anterior cruciate ligament rupture).
Furthermore, in 1 knee, there was an aseptic bone necrosis of the lateral femoral condyle. Knees with previous fractures were excluded. TKAs with all 3 components
cemented included Duracon modular (Howmedica Inc. Rutherford, NJ/International division of Pfizer, n=50), NexGen (Zimmer, Warsaw, IN, USA, n=30), AMK prostheses (DePuy, Warsaw, IN, USA n=14) or AGC (Biomet Merck Limited, Bridgend, South Wales, UK, n=1) prostheses. To assess the effect of me-chanical axis correction in the tibial BMD (original publication I), we divided these patients according to their preoperative long-standing radiographs into preopera-tive varus and valgus groups. The varus group was further divided into subgroups reflecting the postoperative radiological status (residual varus (over 3 degrees of varus), straight or overcorrection to valgus (over 3 degrees of valgus) axis).
The second subgroup consisted of 26 patients, who were recruited from the Kuopio University Hospital Orthopedic Department between May 15th, 1998 and March 16th, 2000. All twenty-six patients were enrolled into the study, and were randomized into two treatment groups by study nurses with a closed envelope method. All orthopedic surgeons who either operated on or examined the patients during the follow-up were blinded to the allocation. Medication was initiated after surgery. Initially, fourteen patients received alendronate (Fosamax, Merck & Co., Inc., NJ, USA), at a dose of 10mg/day orally in the morning, and calcium carbonate (Calcichew, Nycomed Pharma, Nycomed Amesham, Oslo, Norway), at a dose of 500mg/day orally, in the afternoon or evening. The other group of twelve patients received only calcium carbonate at a dose of 500mg/day. Alendronate was swal-lowed on an empty stomach with a full glass of plain water. The patient flow of this study is described in detail in Figure 3.
The third subgroup consisted of thirty-eight patients. Thirty-five of these pa-tients had a knee with primary OA and two with posttraumatic OA (not including prior bone-affecting traumas, only open or arthroscopic meniscectomy). One pa-tient had a bone necrosis of the lateral femoral condyle. In this study setting, joint replacements of the contralateral knee or either hip before the scheduled surgery or during the whole follow-up period of four years postoperatively, were exclusion
criteria. Figure 3. Patient flow chart in bisphosphonate and control groups in the first seven years
following total knee arthroplasty (TKA; DXA, dual-energy X-ray absorptiometry).
The baseline characteristics of the patients in these three subgroups, together with their American Knee Society (AKS) scores (Insall, et al. 1989), are presented in Table I.
cemented included Duracon modular (Howmedica Inc. Rutherford, NJ/International division of Pfizer, n=50), NexGen (Zimmer, Warsaw, IN, USA, n=30), AMK prostheses (DePuy, Warsaw, IN, USA n=14) or AGC (Biomet Merck Limited, Bridgend, South Wales, UK, n=1) prostheses. To assess the effect of me-chanical axis correction in the tibial BMD (original publication I), we divided these patients according to their preoperative long-standing radiographs into preopera-tive varus and valgus groups. The varus group was further divided into subgroups reflecting the postoperative radiological status (residual varus (over 3 degrees of varus), straight or overcorrection to valgus (over 3 degrees of valgus) axis).
The second subgroup consisted of 26 patients, who were recruited from the Kuopio University Hospital Orthopedic Department between May 15th, 1998 and March 16th, 2000. All twenty-six patients were enrolled into the study, and were randomized into two treatment groups by study nurses with a closed envelope method. All orthopedic surgeons who either operated on or examined the patients during the follow-up were blinded to the allocation. Medication was initiated after surgery. Initially, fourteen patients received alendronate (Fosamax, Merck & Co., Inc., NJ, USA), at a dose of 10mg/day orally in the morning, and calcium carbonate (Calcichew, Nycomed Pharma, Nycomed Amesham, Oslo, Norway), at a dose of 500mg/day orally, in the afternoon or evening. The other group of twelve patients received only calcium carbonate at a dose of 500mg/day. Alendronate was swal-lowed on an empty stomach with a full glass of plain water. The patient flow of this study is described in detail in Figure 3.
The third subgroup consisted of thirty-eight patients. Thirty-five of these pa-tients had a knee with primary OA and two with posttraumatic OA (not including prior bone-affecting traumas, only open or arthroscopic meniscectomy). One pa-tient had a bone necrosis of the lateral femoral condyle. In this study setting, joint replacements of the contralateral knee or either hip before the scheduled surgery or during the whole follow-up period of four years postoperatively, were exclusion
criteria. Figure 3. Patient flow chart in bisphosphonate and control groups in the first seven years
following total knee arthroplasty (TKA; DXA, dual-energy X-ray absorptiometry).
The baseline characteristics of the patients in these three subgroups, together with their American Knee Society (AKS) scores (Insall, et al. 1989), are presented in Table I.
Table I. General patient characteristics of the the subgroups I-III (mean and standard devia-tion as appropriate).
*p-value between the alendronate + calcium and calcium groups. Chi squared test
†p-value between the alendronate + calcium and calcium groups. Unpaired t-test
The fourth subgroup consisted of eighteen patients, 10 male and 8 female, who were scheduled for revision arthroplasty of primary knee prostheses. Seventeen revision procedures were performed at this subgroup between March 2012 and February 2013. There was a patellar component in six of these knees. The main in-dications for revision surgery were instability (7 out of 18 knees, 38.9%), suspicion of aseptic loosening (4 out of 18, 22.2%), and patellar luxation (2 out of 18, 11,1%).
Other reasons were pain (1), stiffness (1), suspected polyethylene wear (1) and malalignment (1). In one of the patients suffering a patellar fracture, the revision operation was canceled. A revision of one or more components was performed for seven of the patients (41.2% of the operated knees). An exchange of the tibial poly-ethylene insert only was performed for five patients (29.4%). The other revision procedures were performed once each (3.8%). The baseline characteristics of these patients, together with their AKS scores, revision indications and final operations performed are presented in Table II.
Tibial BMD subgroup (I) Alendronate subgroup (II) Hips and contralateral knee BMD subgroup (III) Baseline
charac-teristics Preopera-tive varus knees
Preoperative
valgus knees Alendronate
+ calcium Calcium
No of patients 67 19 12 14 38
No of knees
operated 75 20 12 14 38
Male/Female 23/52 1/19 4/8 5/9 *1.000 7/31
Age years (SD) 68 (6.6) 67 (7.4) 66 (7.0) 68 (8.2)†0.269 68 (6.7) Body mass index
(SD) 30 (4.5) 28 (5.5) 29.0 (3.8) 29.8 (3.6)†0.577 29.8 (5.2) Preoperative
AKS score (SD) 93 (30.4) 100 (39.1) 106 (30.6) 97 (20.9)†0.391 91 (37.2)
Table II. General characteristics of the 17 revision knee arthroplasty patients. The number of patients for the different indications for revision, the mean age (standard deviation, SD), gender, mean American Knee Society (AKS) scores (SD) and final operations performed are presented.
Indication N:o of pa-tients
Age mean (+SD)
Male/ Female
AKS mean
(+SD) Operation
Instability 7 61 (7.0) 5/2 116 (32.1) Polyethylene change n=5 plus patellar resurfacing n=1 Component revision n=1 Aseptic
loosen-ing 4 72 (8.1) 1/3 79 (37.4) Component revision
Patellar
luxa-tion 2 68 (7.8) 2/0 97 (23.3) Medial patellofemoral
liga-ment reconstruction n=1 Partial patellar resection plus
polyethylene change n=1
Pain 1 47 1/0 125 Patellar resurfacing
Stiffness 1 74 1/0 159 Debridement, polyethylene
change, patellar re-resurfacing n=1 Polyethylene
wear 1 53 0/1 65 Component revision
Malalignment 1 75 0/1 90 Component revision
Total 17 65 (9.8) 10/7 104 (35.1) n=17
Table I. General patient characteristics of the the subgroups I-III (mean and standard devia-tion as appropriate).
*p-value between the alendronate + calcium and calcium groups. Chi squared test
†p-value between the alendronate + calcium and calcium groups. Unpaired t-test
The fourth subgroup consisted of eighteen patients, 10 male and 8 female, who were scheduled for revision arthroplasty of primary knee prostheses. Seventeen revision procedures were performed at this subgroup between March 2012 and February 2013. There was a patellar component in six of these knees. The main in-dications for revision surgery were instability (7 out of 18 knees, 38.9%), suspicion of aseptic loosening (4 out of 18, 22.2%), and patellar luxation (2 out of 18, 11,1%).
Other reasons were pain (1), stiffness (1), suspected polyethylene wear (1) and malalignment (1). In one of the patients suffering a patellar fracture, the revision operation was canceled. A revision of one or more components was performed for seven of the patients (41.2% of the operated knees). An exchange of the tibial poly-ethylene insert only was performed for five patients (29.4%). The other revision procedures were performed once each (3.8%). The baseline characteristics of these patients, together with their AKS scores, revision indications and final operations performed are presented in Table II.
Tibial BMD subgroup (I) Alendronate subgroup (II) Hips and contralateral knee BMD subgroup (III) Baseline
charac-teristics Preopera-tive varus knees
Preoperative
valgus knees Alendronate
+ calcium Calcium
No of patients 67 19 12 14 38
No of knees
operated 75 20 12 14 38
Male/Female 23/52 1/19 4/8 5/9 *1.000 7/31
Age years (SD) 68 (6.6) 67 (7.4) 66 (7.0) 68 (8.2)†0.269 68 (6.7) Body mass index
(SD) 30 (4.5) 28 (5.5) 29.0 (3.8) 29.8 (3.6)†0.577 29.8 (5.2) Preoperative
AKS score (SD) 93 (30.4) 100 (39.1) 106 (30.6) 97 (20.9)†0.391 91 (37.2)
Table II. General characteristics of the 17 revision knee arthroplasty patients. The number of patients for the different indications for revision, the mean age (standard deviation, SD), gender, mean American Knee Society (AKS) scores (SD) and final operations performed are presented.
Indication N:o of pa-tients
Age mean (+SD)
Male/
Female
AKS mean
(+SD) Operation
Instability 7 61 (7.0) 5/2 116 (32.1) Polyethylene change n=5 plus patellar resurfacing n=1 Component revision n=1 Aseptic
loosen-ing 4 72 (8.1) 1/3 79 (37.4) Component revision
Patellar
luxa-tion 2 68 (7.8) 2/0 97 (23.3) Medial patellofemoral
liga-ment reconstruction n=1 Partial patellar resection plus
polyethylene change n=1
Pain 1 47 1/0 125 Patellar resurfacing
Stiffness 1 74 1/0 159 Debridement, polyethylene
change, patellar re-resurfacing n=1 Polyethylene
wear 1 53 0/1 65 Component revision
Malalignment 1 75 0/1 90 Component revision
Total 17 65 (9.8) 10/7 104 (35.1) n=17