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Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_22 | Pages 9 - 9
1 May 2013
Schmalzried T
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First, we need to define “contemporary UHMWPE”. Then we can discuss whether or not this is “the ultimate bearing partner”. The essential criterion for contemporary UHMWPE is intentional crosslinking. There are a number of such acetabular bearing products in the worldwide marketplace. They can differ in several ways including the base resin, the method of consolidation, the method of crosslinking, remelting v. annealing, the packaging and method of sterilisation, and the incorporation of any antioxidant. Thus “contemporary UHMWPE” is not one material, but a family of materials that may have some practical (clinical) differences. There is one essential similarity: substantially reduced wear and osteolysis compared to UHMWPE that is not intentionally crosslinked.

In one literature review, Kurtz et al. reported a weighted-average femoral head penetration rate (wear) for crosslinked acetabular bearings of 0.042 mm/year based on 28 studies (n = 1,503 hips) and 0.137 mm/year for non-crosslinked bearing based on 18 studies (n = 695 hips). The pooled odds ratio for the risk of osteolysis in crosslinked versus conventional liners was 0.13 (95% CI, 0.06–0.27) among studies with minimum 5-year follow-up. Reduction in femoral head penetration or osteolysis risk was not established for large-diameter (>32 mm) femoral heads. In another minimum 5 year follow-up study, Lachiewicz et al. reported that there was no hip with pelvic or femoral osteolysis. They found no association between femoral head size and the linear wear rate, but observed an association between larger (36- and 40-mm) head size with higher volumetric wear rate and higher total volumetric wear.

Leung et al. compared wear, osteolysis incidence, location, and volume on CT scans between 40 hips with non-crosslinked UHMWPE and 36 hips with crosslinked UHMWPE, at a minimum of 5 years. The incidence of osteolysis was statistically greater for patients with non-crosslinked UHMWPE (11/40, 28%) compared to patients with crosslinked UHMWPE (3/36, 8%; P = 0.04). The average lesion volume for hips with non-crosslinked liners (7.5 ± 6.7 cm3) was significantly greater than the average lesion volume for hips implanted with crosslinked liners (1.2 ± 0.1 cm3, P = 0.01).

Bragdon et al. combined a single-centre and two multicentre studies to include 768 primary patients (head size 26–36 mm) with a minimum of 7 years follow-up. Serial plain radiographs showed no osteolysis. The average femoral head penetration rates did not correlate with time in vivo for patients with standard femoral head sizes. There was an indication of higher wear in patients with 36-mm diameter bearings; it was below the threshold for producing osteolysis.

Battenberg et al. quantified the activity of 14 healthy patients with a well-functioning THA at two time periods: early (within 3.5 years of implantation) and late (10–13 postoperative years). Wear was measured on serial radiographs using edge detection-based software. Mean activity decreased by 16% from the early to the late period. Mean gait speed decreased by 9%. Gait speed was 26% slower for patients ≥65 years than for patients <65 years. The mean linear penetration rate decreased by 42% from the first 5 years (early wear rate) to the next 8 years (late wear rate, 5–13 years): 0.043 mm/year to 0.025 mm/year. The greatest patient activity and wear occur during the first 5 years. Walking speed and gait cycles both decreased with aging, resulting in deceasing wear and risk of osteolysis over time.

Crosslinked UHMWPE has consistently demonstrated decreased wear and osteolysis with up to 13 years follow-up. Volumetric wear is increased with larger diameter bearings but appears to be below the osteolysis threshold for most hips, especially considering that patient activity decreases with their aging.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_22 | Pages 35 - 35
1 May 2013
Schmalzried T
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The elements of my routine pre-op. planning include skin and scar assessment, the limb length (physical exam and radiographic assessments), the socket type, the stem type, and radiographic templating. Blood management is rarely an issue for primary total hips today and I generally do not recommend pre-operative autologous donation. I currently use a low molecular weight heparin for venous thromboembolic prophylaxis for most all patients. All of my patients have pre-operative medical clearance from a hospital intensivist.

A press-fit modular cementless socket is my “workhorse,” although I occasionally use supplemental fixation with spikes (low bone density) or screws (shallow or otherwise deficient hemisphere). Cemented fixation is reserved for hips with radiation necrosis. I use a dual-offset tapered cementless stem in most cases but will use a modular stem in dysplastic, post-traumatic, or severely osteoporotic femurs.

I template every case. My goals are to determine component sizes - “the part inside the bone” and improve the biomechanics of the hip – “the part outside the bone”. Sizing is relatively straight forward. For the socket, I use the teardrop and the superior bony edge as landmarks for size and position. I use a Johnson's lateral view radiograph to assess socket version and anterior osteophytes. With a tapered stem, proximal fit on the AP radiograph is the goal and the stem does not need to be canal filling. For the neck resection, I reference off the lesser trochanter.

Medialisation of the hip centre of rotation (COR) decreases the moment arm for body weight; increasing the femoral off-set lengthens the lever arm for the abductor muscles. These changes in hip biomechanics have a double benefit: a reduction in required abductor forces and lower joint reaction forces. There is accumulating clinical evidence that such favourable alterations in biomechanics can improve clinical outcomes and reduce wear. Higher femoral off-set has been associated with greater hip abduction motion and abductor muscle strength. In two independent studies, higher femoral off-set has been associated with a significant reduction in polyethylene wear.

The traditional arthroplasty goal has been to re-create the off-set of the operated hip. In an analysis of 41 patients with one arthritic hip and one clinically and radiographically normal hip (Rolfe et al., 2006 ORS), we found that the horizontal femoral off-set of the arthritic hip was, on average, 6 mm less than that of the normal, contralateral hip. Considering this, and with medialisation of the COR, is it reasonable to make the femoral off-set a few millimeters greater than that pre-op. With modular trial components, final off-set and limb-length adjustments are made intra-operatively by assessing soft tissue tension, joint stability and range of motion.

Applying these principles in a consecutive series of 40 hips, the hip centre of rotation was medialised by 5.6 mm and the horizontal femoral off-set was increased by an average of 9.5 mm, being larger than the normal, contralateral hip by an average of 5.2 mm. This combination increased the net biomechanical advantage of the diseased hip to an average of 12.5% more than the normal, contralateral hip. The increase in femoral off-set is compensated for by medialising the COR. The average lateralisation of the proximal femur of 3.9 mm did not cause trochanteric bursitis or other pain. When the offset is right, soft tissue tension can be maintained without over-lengthening. In this series, 2.9 mm average lengthening resulted in the reconstructed limb being an average of 1.1 mm shorter than the normal side.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 295 - 295
1 May 2010
Bitsch R Loidolt T Lürssen M Jäger S Heisel C Schmalzried T
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Introduction: In recent retrieval studies over-penetration of cement, incomplete seating of the prosthesis with a resultant polar cement mass, or both, have been associated with femoral failures of current generation resurfacing arthroplasties. We developed a laboratory model to analyze differences in cement penetration, cement pressures and interface temperatures for hip resurfacing arthroplasty.

Materials and Methods: A carbon foam was demonstrated to closely simulate human femoral heads. Custom aluminum shells were made by DePuy with the same inner geometry as the femoral resurfacing components. (ASR™ system, Size 49, DePuy; Leeds, England).

Analyses of six different cementing techniques (cemtech) were performed using high viscosity (HVC) (Smart Set GHV, DePuy, Blackpool, England) and low viscosity cement (LVC) (Endurance, DePuy, Blackpool, England):

Manual application HVC

¼filling of the component with LVC and manual appl.

¼filling HVC and manual appl.

½filling LVC

½filling HVC

Complete filling with LVC

A force of 150N was used to press five shells in each cemtech group on foam specimens. During seating cement pressures and polymerization heat 5 mm under the foam surface were measured.

Specimens were cut into quarters, surfaces were digitalized and cement penetration areas and depths were quantified using a pixel-analysis-software. The effects of the cemtech were examined by Kruscal-Wallis and Mann-Whitney-U-tests (two-sided, p-value< 0.05, SPSS)

Results: The mean cement pressures increased going from cemtech A to E. HVC cemtech C and E showed higher pressures than the comparable LVC cemtech B and D.

Maximum temperatures were A) 36.0± 4.1°C, B) 45.0±5.7°C, C) 36.2±4.2°C, D) 53.5±2.5°C, E) 48.3±6.5°C and F) 53.2±12.6°C. D, E and F exceeded 50°C.

A provided even cement penetration over the available fixation area without involvement of the internal area and the stem. Cemtech that used LVC cement (B, D and F) showed higher interior area cement contents than HVC (A, E and C). The cement content in the interior area was A) 39.3±26.4mm2, B) 72.1±16.9mm2, C) 37.7±10.5mm2, D) 99.0±24.6mm2, E) 67.5±15.6mm2 and F) 121.0±29.0mm2.

A showed mainly complete seating with a cement mantle thickness of 0.5±0.7 mm. All other cemtech had incomplete seating in all specimens with significantly thicker polar cement mantles (p=0.032) up to a maximum of 4.6±1.2mm for E.

Discussion: Component filling cemtech and LVC resulted in variable degrees of over-penetration, exposure to high temperatures or a risk for incomplete seating, which have been associated with bone necrosis and early fracture. The use of the manual application and HVC cement showed clear advantages in our model. It was possible to utilize all of the available fixation area without negative effects.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 75 - 75
1 Mar 2006
Heisel C Silva M Skipor A Jacobs J Schmalzried T
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Background: Metal-metal bearings are frequently implanted in young, active patients. The relationship between patient activity and Co and Cr ion levels has not been scientifically investigated.

Methods: Seven patient subjects with well-functioning metal-metal bearing hip prostheses and one control subject (no implants), all with normal renal function, were monitored during a two-week long activity protocol. Lower extremity activity was continuously assessed by a computerized, two-dimensional accelerometer (Step Activity Monitor; SAM). During the first week, subjects were requested to limit physical activity. Subjects then completed an hour-long treadmill test followed by a week where they were encouraged to be as physically active as possible. Serum Co and Cr ion levels and urine Cr levels were assessed at 10 different time points during these two weeks.

Results: Regardless of activity, the serum ion levels for a given patient were essentially constant and there was no correlation between patient activity and serum or urine ion levels. A mean increase in activity of 28% (95% CI, 13 to 43%; SE, 6%) during the high-intensity activity week resulted in a mean decrease of 2.6% (95% CI, −14.2 to 8.9%; SE, 4.7%) in serum Co and a mean increase of 2.0% (95% CI, −5.3 to 9.3%; SE, 3.0%) in serum Cr. During the treadmill test, a mean activity increase of 1,621% (16-fold) (95% CI, 972 to 2,271%; SE, 265%) resulted in a mean increase of 3.0% (95% CI, −5.7 to 11.7%; SE, 3.6%) in serum Co and a mean increase of 0.8% (95% CI, −3.5 to 5.0%; SE, 1.7%) in serum Cr. This effectively constitutes no change in serum ion levels for these changes in activity because the differences are within the variability for the measurement accuracy of these tests.

Conclusions: In patients with normal renal function and a well-functioning metal-metal bearing, ion levels are not affected by patient activity. Periodic measurements of serum ion levels can be used to monitor the tribologic performance of prosthesis with a metal-metal bearing without adjusting for patient activity.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_IV | Pages 452 - 452
1 Apr 2004
Streicher R Banks S Schmalzried T Reilly D
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Sagittal knee implant design, together with soft tissue and alignment, determines the kinematics of an artificial knee joint. A single-radius design was thought to improve the kinematics and biomechanics of a knee joint prosthesis and therefore also improve rehabilitation. Two total knee joint prosthesis designs, differing only in their sagittal geometry, were compared in vivo.

To determine the three-dimensional kinematics and difference between a multi-radius and single-radius implants, six patients, all one-year postoperative, were subjected to video-fluoroscopy while walking on a treadmill, stepping up and down a 20-cm step and doing deep lunges.

In a clinical evaluation, differences in range of motion, functional knee score, 40-cm chair raise and anterior pain at 6 weeks and 3, 6 and 12 months were compared in 86 patients with multi-radius and 108 patients with single-radius implants. The age of the patients in the two groups was similar and ranged from 68 to 70 years.

Fluoroscopically-determined flexion was 105° in the multi-radius group and 123° in the single-radius group (p < 0.01). External rotation and lateral condyle movement was statistically similar. The single-radius group did not exhibit paradoxical motion of the medial condyle and had less overall movement. The objective knee scores did not differ significantly (p > 0.05). Patients in the single-radius group gained flexion significantly faster (p < 0.001). After one year, there was no difference between the groups. Three months postoperatively, 72% of the single-radius group could rise from a chair without using their arms, compared to 40% of the multi-radius group (p < 0.001). Although this improved in both groups, it remained superior in the single-radius group. Anterior knee pain was present in 59% of the multi-radius group and in only 18% of the single-radius group at three months (p < 0.001). At one-year follow-up, 4% of the single-radius and 29% of the multi-radius groups respectively complained of anterior knee pain (p < 0.001).

A single-radius sagittal design knee prosthesis leads to faster rehabilitation better and kinematics than a multi-radius design. The reduced movement of the condyles on the polyethylene insert should result in less long-term wear.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_IV | Pages 404 - 405
1 Apr 2004
Silva M Jackson W Shepherd E Rosa MD Schmalzried T
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Introduction: The Step Activity Monitor (SAM) is a microprocessor worn on the ankle that measures ambulatory activity in real time.

Methods: Activity magnitudes, speed parameters and activity patterns were analyzed in 31 patients with 37 primary total hips. Wear was measured from digitized radiographs using a validated two-dimensional, edge detection-based computer algorithm.

Results: On average, patients walked 5.6 hours per day (range: 1.9–9.8); averaging 5,266 gait cycles (range: 1,737–11,805), at 20 cycles/minute (range: 12.7–32.8) with a maximum speed of 63 cycles/minute (range: 45.0–88.0). Fast and very fast walking (30–49 and > 50 cycles/minute) accounted for 9.4% and 4.4% of total walking time. Patients started and stopped walking about 66 times per day (range: 34–113), with about 81 cycles between stops (range: 28.1-200.1) in average active intervals of 5.3 minutes (range: 3.3–10.3).

There was no difference in the average number of gait cycles between females and males. However, polyethylene wear per million cycles was significantly higher in males (p=0.006). Even after adjustment for greater height and weight in males, their wear rate was still significantly higher (p< 0.01). Males walked at a higher average speed (p=0.07), spent 33.9% more time walking fast or very fast, had 4% more starts/stops per day, with 13% less strides between stops. The percentage of time spent walking slow (5–9 cycles/minute) was negatively correlated to wear (p< 0.05).

Discussion and Conclusion: The SAM allows assessment of patterns and intensity of joint use. Similar to a set of automobile tires, polyethylene wear is a function of the amount and type of use; faster walking with more frequents starting and stopping is associated with a higher polyethylene wear rate. As the clinical performance of crosslinked polyethylenes is being monitored, it is critical to consider the influence of the amount and type of patient activity on wear.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 24 - 24
1 Jan 2004
Beaule P Schmalzried T Dorey F Amstutz H
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Purpose: Treatment of Ficat III and IV femoral head necrosis is a serious challenge and a controversial issue due to the young age of the patients and disappointing results obtained with total hip arthroplasty (THA). We reviewed our experience with the cemented adjusted cup to identify factors leading to surgical revision and assess long-term clinical outcome.

Material and methods: Sixty hips presenting necrotic heads were treated by cemented adjusted cups. Mean age of the patients was 33.6 years (range 18–51); 23% women and 77% men. The Ficat classification was: grade II 6%, grade III 85%, grade IV 9%. Mean necrotic Kerboull angle was 192°. In addition, the status of the acetabular cartilage was recorded at surgery: grade I normal 17%, grade II fissuration 30%, grade IIIA fibrillation without osteophytes 28%, grade IIIB fibrillation with osteophytes 10%, grade IV partial erosion reaching subchondral bone 10%.

Results: At mean follow-up of 7.8 years (range 1 – 21 years), there were no cases of dislocation, femur neck fracture, or osteolysis. Mean UCLA score showed significant improvement in pain (from 4.5 to 8.1), walking (6.1 to 8.8), function (5.3 to 7.6), and activity (4.2 to 5.8). Five-, ten-, and fifteen-year survival rates were 81, 57, and 40% respectively. Fifteen hips required THA, twelve for acetabular cartilage wear, one for femoral loosening, and one for infection. A positive correlation (p = 0.005) was observed between the duration of signs preoperatively and degradation of the acetabular cartilage, suggesting a relationship also with shorter prosthesis survival. The Kerboull necrosis angle and Ficat grade were not correlated with prosthesis survival.

Discussion: Survival of the adjusted cup is better when symptoms have been perceptible for less than one year, probably because the acetabular cartilage is less damaged. These results are better than those with other conservative solutions such as osteotomy or vascularised graft which do not reach 80% survival at five years and which provide less effective pain relief. If necessary, conversion to a THA can be performed without compromising clinical outcome.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 185 - 185
1 Jul 2002
Schmalzried T
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Modular polyethylene acetabular bearings were initially introduced in conjunction with a metal-backed component designed for fixation with cement. It was anticipated that aseptic loosening would be eliminated by the new metal-backed component. A modular liner would allow a simple exchange of the bearing when it was worn. Although this technique has rarely been used with cemented sockets, the concept of modularity had merit for cementless sockets. Early studies of cementless sockets indicated that initial implant stability and increased bone ingrowth occurred with screw fixation. A modular liner allowed screws to be placed through the socket.

First-generation modular components were variably plagued by mechanically insufficient locking mechanisms, insufficient support of the poly by the metal shell, insufficient polyethylene thickness (variably oxidized) and excessive motion between the liner and the shell leading to an array of complications including frank dissociation of the liner, back-side wear, generally higher wear rates and more osteolysis, especially retro-acetabular.

There is nothing inherently good or bad about modularity; it wholly depends on how it is done. More recent offerings have, at least in theory, addressed the limitations of earlier designs. Current designs are characterised by stronger locking mechanisms and reduced liner-shell motion. Most systems offer choices for initial fixation (press-fit, screws, spikes, etc.), bearing diameters, and face geometries (neutral, face-changing, lipped or hooded). Some systems offer a choice of bearing material (polyethylene(s), metal, ceramic). It will simply take time to learn which material, design, and manufacturing advances translate into long-term clinical success.

In an era of hip arthroplasty featuring more wear resistant bearings, it is reasonable to question whether or not modularity is necessary. If satisfactory fixation can be obtained with a simple press-fit and the wear resistance of the bearing is high enough to last the patient’s lifetime, why not use a non-modular component? Modularity allows intraoperative flexibility at the primary surgery and in the event a revision is required. Further, it is not yet known if any or all of the new bearings will demonstrate the anticipated in vivo wear resistance.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 183 - 184
1 Jul 2002
Schmalzried T
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To further extend the longevity of total hip replacement, bearings with better wear characteristics are desirable. Despite generally inferior clinical results with metal-on- metal total hip replacements, many metal-on-metal implants lasted over two decades or are still functioning in patients who received the implant at a young age. Acetabular component wear and loosening limit the survival of hips. Because of this, long-term survival rates of the Charnley hip and the McKee-Farrar are similar. Consequently, there is renewed interest in metal-on- metal bearings for total hip arthroplasty.

Aseptic loosening of early metal-on-metal prostheses was not uniform due to the metal-on-metal bearings or due to wear. There is evidence indicating that some metal-on-metal bearing couples were poorly designed and/or manufactured leading to high frictional torque and/or excessive wear which could have been the cause of failure. Very low wear has been observed on metal-on- metal bearings retrieved after more than 20 years of use. The wear characteristics are a function of materials, design, and manufacturing. Polar bearing is preferred to reduce frictional torque, but excessive radial clearance is associated with higher wear. As has been demonstrated in hips with metal-on-plastic bearings, clinical success and failure are multifactorial. The chance of success with new metal-on-metal bearings is increased when the bearing is combined with well-established femoral stems and acetabular shells. As has been seen in hips, which have metal-on-polyethylene bearings, loosening of hips with metal-on-metal bearings can occur due to other factors such as suboptimal stem and/or cup design, manufacturing or implantation technique.

Studies of the levels of cobalt and chromium in the hair, blood, and urine have shown that metallic content in patients with metal-metal total hips are generally higher than in patients with metal-UHMWPE articulations. While the release of cobalt and chromium ions from metal-metal total hips has been verified, the clinical significance of this finding is still unclear. Cobalt and chromium wear particles have been shown to induce carcinoma in animal models, giving rise to the concern that such alloys could have the same effect if present in sufficient amounts in human tissue for a sufficient length of time. Overall, the available epidemiological data do not demonstrate an increase in cancer risk following total hip replacement. At the same time, it is important to recognise the limitations of the available data with regard to sample size, length of follow-up and lack of stratification for other co-morbidities.

The issue of delayed-type hypersensitivity (DTH) to the main elements in metal-metal total hips – cobalt, chromium, and nickel. Skin patch testing is unreliable for the assessment of hypersensitivity to implants, however, this type of testing has shown that cobalt, chromium, and nickel are associated with contact dermatitis. Because there is a higher reported incidence of metal sensitivity in patients with loose components, the association between metal sensitivity and loose implants has fuelled a long-standing debate: does hypersensitivity cause loosening or does loosening cause hypersensitivity? A small number of patients with metal-metal total hips develop an adverse local tissue response and present with unexplained pain and chronic effusions that resolve when the metal-metal bearings are exchanged for metal-UHMWPE hips. The histology of abundant lymphocytes and plasma cells is highly suggestive of an immune response. Caution should be taken in the implantation of a metal-metal bearing in patients with a known sensitivity to metals.

Further investigations of the local and systemic effects related to the wear of the primary articulating surfaces are needed. It should be emphasised, however, that clinical success is multifactorial. Patient selection, surgical technique, component fixation, and the other aspects of the prosthetic joint will influence the clinical performance of any articulation.


The Journal of Bone & Joint Surgery British Volume
Vol. 76-B, Issue 3 | Pages 423 - 427
1 May 1994
Amstutz H Grigoris P Safran M Grecula M Campbell P Schmalzried T

Cemented Ti-6Al-4V components were used to resurface ten femoral heads in nine young adult patients with osteonecrosis of the femoral head (average age 32 years; range 20 to 51). There were eight hips at Ficat stage III and two at stage IV. Five hips have maintained satisfactory function for an average period of 11.2 years (10 to 12.2) with no radiographic evidence of component loosening or osteolysis; five have been revised after an average period of 7.8 years (3.3 to 10.3) for pain caused by deterioration of the acetabular cartilage. No component required revision for loosening and the specimens retrieved at revision showed no evidence of osteolysis despite burnishing of the titanium bearing surface and the presence of particulate titanium debris in the tissues.


The Journal of Bone & Joint Surgery British Volume
Vol. 75-B, Issue 6 | Pages 980 - 981
1 Nov 1993
Schmalzried T


The Journal of Bone & Joint Surgery British Volume
Vol. 75-B, Issue 4 | Pages 608 - 615
1 Jul 1993
Schmalzried T Harris W

We have reviewed 97 consecutive primary hip replacements with a cemented femoral component and a porous-ingrowth acetabular component at a minimum five-year follow-up (average 6.5 years). The average Harris hip score was 93, and 85 hips had no pain or only slight pain. There had been no deterioration in the results since the two-year follow-up. The hybrid hip is successful for up to eight years and appears to be suitable for many patients. Long-term femoral fixation has been shown to improve with second-generation cementing techniques and in this series was excellent with third-generation techniques, in that only one stem was revised for loosening. No cementless acetabular component was revised for loosening.


The Journal of Bone & Joint Surgery British Volume
Vol. 75-B, Issue 1 | Pages 161 - 162
1 Jan 1993
Campbell P Kossovsky N Schmalzried T


The Journal of Bone & Joint Surgery British Volume
Vol. 68-B, Issue 4 | Pages 635 - 642
1 Aug 1986
Nilsson O Urist M Dawson E Schmalzried T Finerman G

In dogs, resection of a length of the ulna equal to twice the diameter of the mid-shaft leaves a defect which consistently fails to unite. In response to an implant of 100 mg of bovine bone morphogenetic protein (BMP), the defect becomes filled by callus consisting of fibrocartilage, cartilage and woven bone within four weeks. The cartilage is resorbed and replaced by new bone in four to eight weeks. Woven bone is then resorbed, colonised by bone marrow cells and remodelled into lamellar bone. Union of the defect is produced by 12 weeks. Control defects filled with autogeneic cortical bone chips unite after the same period. In regeneration induced by bone morphogenetic protein (BMP) and in repair enhanced by bone graft, union depends upon the proliferation of cells within and around the bone ends. Our working hypothesis is that BMP induces the differentiation of perivascular connective tissue cells into chondroblasts and osteoprogenitor cells and thereby augments the process of bone regeneration from the cells already present in the endosteum and periosteum.