CA2273229A1 - Femur component of a hip joint endoprosthesis - Google Patents

Femur component of a hip joint endoprosthesis Download PDF

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Publication number
CA2273229A1
CA2273229A1 CA002273229A CA2273229A CA2273229A1 CA 2273229 A1 CA2273229 A1 CA 2273229A1 CA 002273229 A CA002273229 A CA 002273229A CA 2273229 A CA2273229 A CA 2273229A CA 2273229 A1 CA2273229 A1 CA 2273229A1
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CA
Canada
Prior art keywords
longitudinal ribs
femur
femur component
plane
symmetry
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
CA002273229A
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French (fr)
Inventor
Walter Moser
Anton Cotting
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Synthes Bettlach GmbH
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Individual
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Filing date
Publication date
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Publication of CA2273229A1 publication Critical patent/CA2273229A1/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/30767Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
    • A61F2/30771Special external or bone-contacting surface, e.g. coating for improving bone ingrowth applied in original prostheses, e.g. holes or grooves
    • AHUMAN NECESSITIES
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    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/32Joints for the hip
    • A61F2/36Femoral heads ; Femoral endoprostheses
    • A61F2/3662Femoral shafts
    • A61F2/367Proximal or metaphyseal parts of shafts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/32Joints for the hip
    • A61F2/36Femoral heads ; Femoral endoprostheses
    • AHUMAN NECESSITIES
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    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/32Joints for the hip
    • A61F2/36Femoral heads ; Femoral endoprostheses
    • A61F2/3662Femoral shafts
    • AHUMAN NECESSITIES
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    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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    • A61F2/36Femoral heads ; Femoral endoprostheses
    • A61F2/3662Femoral shafts
    • A61F2/3676Distal or diaphyseal parts of shafts
    • AHUMAN NECESSITIES
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    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
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    • A61F2002/30317The prosthesis having different structural features at different locations within the same prosthesis
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    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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    • A61F2002/30316The prosthesis having different structural features at different locations within the same prosthesis; Connections between prosthetic parts; Special structural features of bone or joint prostheses not otherwise provided for
    • A61F2002/30317The prosthesis having different structural features at different locations within the same prosthesis
    • A61F2002/30324The prosthesis having different structural features at different locations within the same prosthesis differing in thickness
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    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30316The prosthesis having different structural features at different locations within the same prosthesis; Connections between prosthetic parts; Special structural features of bone or joint prostheses not otherwise provided for
    • A61F2002/30317The prosthesis having different structural features at different locations within the same prosthesis
    • A61F2002/30326The prosthesis having different structural features at different locations within the same prosthesis differing in height or in length
    • AHUMAN NECESSITIES
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    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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    • A61F2/30771Special external or bone-contacting surface, e.g. coating for improving bone ingrowth applied in original prostheses, e.g. holes or grooves
    • A61F2002/30841Sharp anchoring protrusions for impaction into the bone, e.g. sharp pins, spikes
    • A61F2002/30845Sharp anchoring protrusions for impaction into the bone, e.g. sharp pins, spikes with cutting edges
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    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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    • A61F2/30767Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
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    • A61F2002/30878Special external or bone-contacting surface, e.g. coating for improving bone ingrowth applied in original prostheses, e.g. holes or grooves with non-sharp protrusions, for instance contacting the bone for anchoring, e.g. keels, pegs, pins, posts, shanks, stems, struts
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    • A61F2002/30891Plurality of protrusions
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    • A61F2002/3625Necks
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Abstract

The invention relates to a femur component of a hip joint endoprosthesis which has shaft (1) for anchoring in the medullary cavity of the femur. The shaft (1) has a distal section (9) and a proximal section (8), to which is connected a collar section (2) with a peg (3) for receiving an articular head, or with an articular head which is firmly attached to the collar section (2). The shaft (1) comprises a front surface (4), a rear surface (5), a lateral side (6), a medial side (7) and a plane of symmetry (11), whereby longitudinal ribs (10) which stretch from proximal to distal are fitted on the front surface (4) and the rear surface (5) in the proximal section (8) of the shaft (1). The crests (12) of the longitudinal ribs (10) form an angle .delta./2 of at least 1~ to the plane of symmetry (11), and the envelope of the crests (12) of the longitudinal ribs (10) forms a double wedge-like or elliptoide body, which tapers both towards the lateral side (6) and the medial side (7).

Description

1 ; -:~ l~:( ~_;
59-153-3 ,~~
FEMUR COMPONENT OF A HIP-JOINT ENDOPROSTHESIS.
The invention relates to a femur component of a hip-joint endoprosthesis defined in the preamble of claim 1.
s Such femur components already are known from the state of the art, however they incur various drawbacks.
As regards uncemented femur prostheses for hip-joint replacement, the primary stabilization of the femur shaft is implemented by frictionally and geometrically locking onto the enclosing bone. The femur shaft shall be configured in such manner that loading io it will entail its being wedged into the bony support. In particular during the first loading phase wherein some seating shifts of the femur shaft are likely, a corresponding configuration must assure reliable primary affixation. In the event of a seating shift, new stabilization must be assured by corresponding reconfiguration. In the absence of adequate primary stability, loading will entail repeated shifts at the boundary surface ~s between femur shaft and bone, preventing reliable implant bodily incorporation. On the other hand, if the primary anchoring is reliable, the implant can be enclosed by the bone tissue during the healing process and offer good long-term prospects.
Preferably the primary affixation shall be in the upper portion of the prosthesis shaft enclosed by the spongy bone. A large support surface can be achieved in the big bone 2o volume present therein. Seen biomechanically/clinically, it has been advantageous to apply the force through this region.
Illustratively a femur shaft is on the market wherein the proximal shaft portion intended to be anchored in the spongy bone structure continuously tapers sonically in the lateral-to-mesial direction in order to secure renewed, automatic clamping in the event the zs bone would yield in the mesial direction. The region of the trochanter major with the anchoring space however does not have a cross-sectionally triangular or trapezoidal shape, rather an oval one. Accordingly this known femur shaft suffers from the drawback that
2 59-153-3 the laterally much enlarged proximal shaft portion may crack the bone. In addition this known femur shaft comprises solid ribs which when displacing bone volume will raise the pressure and may further contribute to the cracking effect.
A longitudinal section of the proximal femur with inserted femur shaft shows that s the spongy substance is not sharply delimited to the trochanter region but instead partly continues as far as the zone of the diaphyseal bone tube. However as much as possible of this bone structure should be used to transmit the load. But the ribs located in one position of the known femur shaft do not optimally meet this requirement because of the little differentiated configuration. The point of contact and the elongation of the ribs at the io shaft should be designed in such manner that as much as possible of the spongy volume of the proximal femur is used for anchoring.
In this respect, the object of the invention is palliation. The invention addresses the problem of creating a femur component of a hip-joint endoprosthesis optimally corresponding to the spongy architecture in the proximal femur part and entailing is cementless, primary shaft anchoring in the femur in the most stable possible manner to secure thereby good likelihood of bone healing.
The invention solves this problem by a femur component defined by the features of claim 1.
The double-wedge or ellipsoidal shape of the proximal shaft segment offers the zo advantage that the prostheses shaft can wedge itself both laterally and mesially in the event of a seating shift. The oval envelope curve of the ribs matching the cross-section of the proximal femur minimizes the danger of cracking the proximal femur due to direct pressure on the hard cortical bone.
In a preferred further development of the invention, wherein the ribs are cross-2s sectionally triangular, these ribs easily penetrate the spongy bone volume and as a result the pressure is reduced during the insertion procedure. Because preferably the triangular
3 59-153-3 ribs run conically, additional wedging is achieved that is lacking in rectangular ribs such as are used in the state of the art.
The straigthness of the shaft together with the increasing height in the proximal direction of the ribs running in the direction of the shaft axis allows secure positioning and s the femur shaft and knocking it into place with guidance by the self-cutting ribs. If on the other hand the ribs are partly or all mounted at an angle to the shaft axis, no seat enclosing the ribs can be realized when installing the femur shaft. Because the rib projection varies along the shaft, the stress on the spongy volume is more homogeneous than in known shafts with ribs beginning at a given height which then continuously io increases.
Another preferred development consists in that the combs of the longitudinal ribs subtend an angle'/zb of at least 1°, preferably at least 2° with the plane of symmetry. The individual combs of the longitudinal ribs subtend different angles '/zb in the range of 3 to 8° with the plane of symmetry, preferably the longitudinal ribs situated closer to the lateral ~s and the mesial side subtending a larger angle '/zb than those in-between.
Such a rib geometry functionally stimulates the enclosing bone, whereas such a stimulus is not achieved with the dull rib shape of the state of the art. This functional stimulus causes bone regeneration in the stressed zone with ensuing compaction and hence bone healing.
The blood supply to the regenerated bone can optimally form in the troughs of this rib 2o structure.
Appropriately the anterior and posterior surfaces form a wedge tapering toward the distal segment, the central plane being the plane of symmetry, the angle ~ of the wedge being in the range of 0.5 to 3.0°, preferably within 1.0 and 2.0°. On account of this geometry, the wedging effect is continued also along the upper shaft zone. In case sub-zs sequent intervention is due on a solidly integrated shaft, the shaft is more easily knocked free if its geometry is conical in all directions, that is also proximally in the intra-rib zone, than if the geometry were other than conical.
4 59-153-3 Seen in a section orthogonal to the plane of symmetry, the envelope curve of the combs of the longitudinal ribs is approximately in the form of a kite quadrilateral of which the sides may approximately represent straight lines or arcs of circle or elliptical segments.
Relative to the mesial side, the kite quadrilateral should subtend an inside angle a s larger than 10, and preferably larger than 12°. In addition the inside angle a should be less than 22, preferably less than 20°.
Toward the lateral side, the kite quadrilateral should subtend an inside angle ~
larger than 8, preferably larger than 9°. Moreover the inside angle ~3 should be less than 45, preferably less than 40°.
io Appropriately the longitudinal-rib combs are sharp and seen in a section orthogonal to the plane of symmetry are preferably triangular. Illustratively the longitudinal ribs may assume the shape of three-sided pyramids of which the vertices point distally.
The longitudinal-rib combs however may also be rounded and, seen in a section orthogonal to the plane of symmetry, preferably are semi-circular. On the other hand uniformly thick is longitudinal ribs of rectangular cross-section are to be avoided.
Preferably in continuous manner, the width of the longitudinal ribs appropriately decreases from the proximal to the distal sides. This design also applies to the height of the longitudinal ribs which preferably continuously shall decrease in the proximal-to-distal direction.
2o Surprisingly especially good clinical results were observed when at least one of the longitudinal ribs runs as far as the distal half of the shaft because making possible thereby increased primary stability and because bone regeneration or bone transformation propagates proximally from this anchoring zone in the form of osteo-conduction.
Further advantages may be achieved using embodiments wherein the shaft is 2s without collar and assumes a substantially rectangular cross-section as seen in a section orthogonal to the plane of symmetry.

The invention and its further developments are elucidated below in relation to several embodiments shown in the partly schematic Figures.
Fig. 1 is an elevation of the femur component of the invention seen from the anterior side and with two cross-sectional contours, s Fig. 2 is an elevation of the femur component of Fig. 2 seen from the lateral side, Fig. 3 is a section of the femur component of Fig. 1 along line III-III and Fig. 4 is a section similar to that of Fig. 3 with a modified envelope curve of the longitudinal-rib combs.
The femur component of a hip-joint endoprosthesis shown in Figs. 1 through 3 io essentially comprises a shaft 1 without collar with a distal segment 9 and a proximal segment 8 adjoined by a neck 2 with a stub 3 to receive a hinge head, or by a hinge head firmly joining the neck 2. The shaft 1 comprises an anterior surface 4, a posterior surface
5, a lateral side 6, a mesial side 7 and a plane of symmetry 11 identical with the plane of Fig. 1. Shown in a section orthogonal to the plane of symmetry 11, the shaft is of a is substantially rectangular cross-section 14.
Longitudinal ribs 10 are present on the anterior and posterior surfaces 4 and 5 resp.
in the proximal segment 8 of the shaft 1 and run from the proximal side to the distal side.
Depending on their positions, the combs 12 of the longitudinal ribs 10 subtend and an angle '/2b of 3 to 8 ° with the plane of symmetry il. The longitudinal ribs 10 near the zo lateral side 6 and mesial side 7 subtend a larger angle'/zb than the longitudinal ribs 10 in-between. Moreover the individual longitudinal ribs 10 are of different lengths, preferably those located toward the lateral side 6 and the mesial side 7 being shorter than those in between. The line 17 connecting the ends 18 of the longitudinal ribs 10 merging into the anterior and posterior surfaces 4, 5 do not lie on a straight line but instead on a parabolic zs or ellipsoidal curve.

The envelope curves of the combs 12 of the longitudinal ribs 10 subtend a double-wedge or an ellipsoidal body tapering both in the direction of the lateral side 6 and in the direction of the mesial sides 6, 7.
Furthermore the anterior surface 4 together with the posterior surface 5 forms a s wedge 4,5 tapering toward the distal segment 9, the plane of symmetry 11 being the center plane, the wedge angle ~ of the wedge 4, 5 being 0.5°.
As shown in Fig. 3, when seen in a section orthogonal to the plane of symmetry 11, the envelope curve of the combs 12 of the longitudinal ribs 10 form a kite quadrilateral 13, the quadrilateral's short sides pointing laterally and its long sides pointing mesially.
o The inside angle a of the kite quadrilateral 13 is 12 to 20° toward the mesial side 7 and its inside angle (3 toward the lateral side 6 is from 9 to 44°.
The combs 12 of the longitudinal ribs 10 are sharp and when seen in a section orthogonal to the plane of symmetry 11 their contour is triangular. The width and height of the longitudinal ribs 10 decrease continuously in the proximal-to-distal direction.
is Accordingly the longitudinal ribs 12 form three-sided pyramids, the vertex of the pyramid pointing distally. Therefore the troughs between the individual longitudinal ribs 10 narrow from the distal segment 9 to the proximal segment 8.
As shown in Fig. 1, one of the longitudinal ribs 12, namely the center one, runs as far as the distal half of the shaft 1 and thereby enhances the primary stability of the 2o implanted shaft.
The envelope curve of the combs 12 of the longitudinal ribs 10 shown as a kite quadrilateral 13 in Fig. 3 also may comprise slightly outward bulging, for instance arcuate envelope curves 15, as shown in Fig. 4. In this embodiment the angles o and Q
relate to the inside angles of the kite quadrilateral formed by the tangents 16 to the convex 2s envelope curves.

Claims (21)

1. A femur component for a hip-joint endoprosthesis fitted with a shaft (1) to be anchored in the femur's marrow cavity and comprising a distal segment (9) and a proximal segment (8) adjoined by a neck (2) with a stub (3) to receive a hinge head or with a hinge head firmly adjoining the neck (2), further an anterior surface (4), a posterior surface (5) a lateral side (6), a mesial side (7) and a plane of symmetry (11), longitudinal ribs (10) running in the proximal-to-distal direction being present on the anterior surface (4) and on the posterior surface (5) in the proximal segment (8) of the shaft (1), and the envelope curve of the combs (12) of the longitudinal ribs (10) subtending a double-wedge or ellipsoidal body tapering both in the direction of the lateral side (6) and in the direction of the mesial side (7), characterized in that (a) the width of the longitudinal ribs (10) decreases in the proximal-to-distal direction, and (b) the height of the longitudinal ribs (10) decreases in the proximal-to-distal direction.
2. Femur component as claimed in claim 1, characterized in that the combs (12) of the longitudinal ribs (10) subtend an angle 1/2.delta. of at least 1, preferably at least 2°
with the plane of symmetry (11).
3. Femur component as claimed in claim 2, characterized in that the combs (12) of the longitudinal ribs (10) subtend an angle 1/2.delta. in the range of 3 to 8° with the plane of symmetry (11), preferably the longitudinal ribs (10) situated near the lateral side (6) and the mesial side (7) subtending a larger angle 1/2.delta. than do the longitudinal ribs inbetween.
4. Femur components as claimed in one of claims 1 through 3, characterized in that the anterior surface (4) jointly with the posterior surface (5) forms a wedge (4, 5) tapering toward the distal segment (9), where the plane of symmetry (11) is the center plane, said wedge subtending an angle .epsilon. in the range of 0.5 to 3.0 ° and preferably in the range of 1.0 to 2.0°.
5. Femur components as claimed in one of claims 1 through 4, characterized in that the individual longitudinal ribs (10) differ in length between themselves, preferably the longitudinal ribs (10) situated near the lateral side (6) and the mesial side (7) being shorter than the longitudinal ribs (10) in-between.
6. Femur component as claimed in one of claims 1 through 5, characterized in that the combs (12) of the longitudinal ribs (10) are sharp and preferably, when seen in a section orthogonal to the plane of symmetry (11), are triangular.
7. Femur component as claimed in one of claims 1 through 5, characterized in that the combs (12) of the longitudinal ribs (10) are rounded and, as seen in a section orthogonal to the plane of symmetry (11), preferably are semi-circular.
8. Femur component as claimed in one of claims 1 through 7, characterized in that the width of the longitudinal ribs (10) continuously decreases in the proximal-to-distal direction.
9. Femur component as claimed in one of claims 1 through 7, characterized in that the height of the longitudinal ribs (10) continuously decreases in the proximal-to-distal direction.
10. Femur component as claimed in one of claims 1 through 9, characterized in that at least one of the longitudinal ribs (10) runs as far as distal half of the shaft (1).
11. Femur component as claimed in one of claims 1 through 10, characterized in that the kite quadrilateral (13) subtends an inside angle a larger than 10°, preferably larger than 12° with the mesial side (7).
12. Femur component as claimed in one of claims 1 through 11, characterized in that the kite quadrilateral (13) subtends an inside angle a less than 22°, preferably less than 20°, with the mesial side (7).
13. Femur component as claimed in one of claims 1 through 12, characterized in that the kite quadrilateral (13) subtends an inside angle .beta. larger than 8°, preferably larger than 9°, with the lateral side (6).
14. Femur component as claimed in one of claims 1 through 13, characterized in that the kite quadrilateral (13) subtends an inside angle .beta. less than 45°, preferably less than 40° with the lateral side (6).
15. Femur component as claimed in one of claims 1 through 14, characterized in that the shaft (1) is without collar.
16. Femur component as claimed in one of claims 1 through 15, characterized in that the shaft (1) when seen in a section orthogonal to the plane of symmetry (11) is essentially of rectangular cross-section (14).
10 i7. Femur component as claimed in one of claims 1 through 16, characterized in that the longitudinal ribs (12) are in the form of three-sided pyramids of which the vertices point distally.
18. Femur component as claimed in one of claims 1 through 17, characterized in that, when seen in a section orthogonal to the plane of symmetry (11), the envelope curve of the combs (12) of the longitudinal ribs (10) forms a kite quadrilateral (13).
19. Femur component as claimed in one of claims 1 through 17, characterized in that the envelope curve of the combs (12) of the longitudinal ribs (10) when seen in a section orthogonal to the plane of symmetry (11), is lenticular or ellipsoidal.
20. Femur component as claimed in one of claims 1 through 19, characterized in that the connection line (17) of the onset sites (18) of the longitudinal ribs (10) merging into the anterior and posterior surfaces (4, 5) are not rectilinear and preferably are on a parabolic or elliptic curve.
21. Femur component as claimed in one of claims 1 through 20, characterized in that the troughs situated between the individual longitudinal ribs (10) constrict from the distal segment (9) toward the proximal segment (8).
CA002273229A 1996-11-29 1996-11-29 Femur component of a hip joint endoprosthesis Abandoned CA2273229A1 (en)

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AU7616896A (en) 1998-06-22
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ATE294547T1 (en) 2005-05-15
WO1998023231A1 (en) 1998-06-04
AU732409B2 (en) 2001-04-26
EP0942691B1 (en) 2005-05-04
DE59611225D1 (en) 2005-06-09
JP2001505468A (en) 2001-04-24

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