Injectable Cements

Introduction

These cements harden without producing much heat, develop compressive strength, and are remodelled slowly in vivo.

The main purpose of the cement is to fill voids in metaphyseal bone, thereby reducing the need for bone graft, but cements also may improve the holding strength around metal devices in osteoporotic bone.

An ideal cement would be resorbed gradually with time and replaced by host bone.

The rate of cement resorption should be balanced with the rate of new bone formation to avoid collapse at the fracture site, which might occur if resorption is too fast.

 

Proposed benefits of injectable calcium phosphate:

  • When combined with conventional metal fixation in certain fractures (distal radius, tibial plateau, proximal femur, and calcaneus) can produce better stability, stiffness, and strength than metal fixation alone.

  • Early clinical results have shown reduced time to full weightbearing in tibial plateau and calcaneal fractures, more rapid gain of strength and range of motion when used in distal radius fractures, and improved stability in certain hip fractures.

  • Bioactive cements in general also may prove useful in vertebroplasty.

  • Acrylic bone cement (polymethylmethacrylate) enhances fracture stability in patients with osteoporosis. However, polymethylmethacrylate has not gained wide acceptance, because of its exothermic reaction during curing, the inability of the cement to be remodelled, the risk of inhibiting fracture healing if the polymethylmethacrylate is interposed between fracture surfaces, and difficulty in removing the polymethylmethacrylate if revision surgery becomes necessary.

Composition and mechanical properties

At least two types of injectable bioactive cements are being developed.

Bioactive glass ceramic powders with resins

Several formulations of cement in which bioactive glass powders are combined with a bisphenol-a-glycidol methacrylate (Bis-GMA)-based resin have been developed by investigators affiliated with Kyoto University. These cements have been tested in total joint replacement and in the spine. Several formulations of bioactive cements composed of Bis-GMA-based resins mixed with combeite glass-ceramic fillers also are being developed (Cortoss® Synthetic Cortical Bone Void Filler, Orthovita, Inc, Malvern, PA).

 

Calcium phosphate cements

Several calcium phosphate cements are being developed:

Skeletal Repair System (SRS®, Norian Corp, Cupertino, CA)

Norian SRS is delivered as two components:

  • A powder - Mix of monocalcium phosphate, monohydrate, tricalcium phosphate, and calcium carbonate.

  • A fluid - Sodium phosphate solution.

The dry powder and fluid are mixed to form a paste.

The paste is malleable and injectable for approximately 5 minutes.

After injection, the paste hardens within approximately 10 minutes to form a carbonated calcium phosphate apatite (dahllite) of low crystalline order and small crystal size, similar to the mineral phase of bone.

The solubility of the injectable calcium phosphate cement is expected to be similar to that of bone mineral. This means that it will be relatively insoluble at neutral pH and increasingly soluble as pH decreases, an important characteristic of normal bone mineral that facilitates controlled dissolution by osteoclasts.
As it is injected, the cement interdigitates with adjacent bone, forming a solid structure that is more mechanically stable than either cancellous bone graft or the pellets or blocks of hydroxyapatite or calcium sulphate often used to fill metaphyseal defects.

Ten minutes after delivery, the material will have a compressive strength of approximately 10 Mpa. It is important to avoid moving the fracture during these initial minutes to avoid disturbing the material as it sets. The strength of the material increases, and within approximately 12 hours, an ultimate compressive strength of approximately 55 MPa is achieved.

The tensile and shear strength also improve slightly during the course of crystallization, but even when the SRS is cured, these attributes are only 2 to 3 Mpa. This means that fully cured SRS has a compressive strength between that of cancellous and cortical bone, but tensile and shear strength lower than those of cancellous bone.

 

BoneSource® (Howmedica-Osteonics, Rutherford, NJ)

Is a cement with chemistry and physical properties similar to SRS

 

Alpha-BSM® (ETEX Corporation, Cambridge, MA)

Is a calcium phosphate cement with some properties similar to SRS and BoneSource but which seems to have a lower compressive strength and to be absorbed more rapidly in vivo.

 

Histology

Preclinical animal studies have shown that SRS is osteoconductive and undergoes gradual remodeling with time.
There have been several reports of histological evaluation of SRS in humans.

Schildhauer et al described the use of SRS in augmenting internal fixation of calcaneal fractures. Biopsy specimens were obtained from seven patients at the time of hardware removal, more than 1 year after injury. The biopsy specimens showed almost complete bone apposition to the residual SRS. Cement resorbtion was evident in the vicinity of osteoclasts and often was accompanied by new bone formation that appeared qualitatively similar to normal bone remodelling. Vascular ingrowth into the cement was evident, and there was no fibrous tissue.

In studies on femoral neck fractures in human patients, calcium phosphate cement was used for augmentation around cannulated screws used for internal fixation. Femoral heads were retrieved from several patients who had nonunion and had total hip arthroplasty. The time from injury was 6 to 28 months. The femoral heads had a complex histological appearance, as is typical in femoral heads that progress to nonunion and avascular necrosis. There were areas with extensive bone apposition to the cement without intervening fibrous tissue, and in other areas, the bone marrow contained macrophages with fragments of cement that had been phagocytosed. In specimens taken from unstable areas that had undergone motion, fragmented SRS and macrophages were prominent. Overall, the histological features showed processes of remodelling identical to those previously reported in animals and similar to those seen in normal bone. However, the study also showed that the cement may fragment if associated with unstable metal hardware.

 

Clinical applications of SRS

SRS augmentation may be appropriate for the repair of fractures of:

Distal Radius

Fractures with severe comminution, bone loss at the fracture site, or involving osteoporotic bone may be difficult to stabilize with plaster alone, and the risk for secondary displacement and malunion is high.

The use of a bioactive cement may make it possible to fill the metaphyseal defect, improve fracture stability, and reduce immobilization time.

In a biomechanical study, Yetkinler et al tested the stability of intraarticular fractures of the distal radius stabilized with Kirschner wires or SRS.

The fractures augmented with cement were significantly more stable and had a significantly higher strength when subjected to cyclic loading and when loaded to failure.
The use of calcium phosphate cement to treat distal radius fractures has been studied for fresh fractures and for fractures that had become displaced after primary treatment with closed reduction and plaster.

In fresh fractures, percutaneous injection of the cement worked well in providing adequate filling of the fracture void. In patients who need a secondary procedure after redislocation while wearing a plaster cast, an open cementing technique that includes evacuating the organized haematoma before injecting the cement was recommended. In a randomized multicenter study of patients with fresh distal radius fractures, cement augmentation combined with a short period of plaster immobilization was compared with conventional external fixation. The group treated with cement augmentation had a significantly faster gain in grip strength and range of movement for the first 8 weeks after the injury, although there were no significant differences later, to a maximum follow up of 1 year.

Similar results were reported in a randomized study on redisplaced fractures of the distal radius where cement augmentation combined with 2 weeks of plaster immobilization was compared with external fixation for 5 weeks.

 

Tibial Plateau

Elevating of depressed articular fragments often reveals a metaphyseal void outlined by crushed cancellous bone. This void commonly is filled with autologous bone graft or with preformed blocks or granules composed of sintered, highly crystalline hydroxyapatite. Although autograft has desirable osteoconductive and osteogenic properties, cancellous bone graft does not provide enough mechanical stability to allow full weightbearing until the fracture has healed. SRS and other injectable bioactive cements, however, can fill the defect completely to produce immediate stability, and they also develop enough compressive strength to facilitate earlier active joint motion and shorter time to full weightbearing than bone graft procedures. In a series of 41 patients with an isolated tibial plateau fracture, Keating and Hajducka allowed free weightbearing 6 weeks after surgery when using SRS to supplement internal fixation in patients with tibial plateau fractures. Despite the early weightbearing, they reported substantial loss of reduction in only one patient, an elderly man with poor compliance.

Metal was used to support the bone–cement construct, but in most cases less metal was required than would have been for fixation without cement augmentation.

 

Calcaneum

It is often a substantial technical challenge to reduce the multiple bone fragments, in addition it often is difficult to maintain joint congruency during healing. The limited stability of the fracture fragments achieved with metal fixation mostly is attributable to the cancellous bone defect that regularly is present under the subtalar joints. This defect seems to be attributable to the crushed cancellous bone, similar to that seen in tibial plateau fractures, made worse by the reduced cancellous bone density commonly found in this part of the calcaneus. When bone graft is used to fill this defect, restricted weightbearing usually is recommended for 8 to 12 weeks.
 

The rationale for using an injectable, bioactive cement in calcaneal fractures is to fill the void under the subtalar joints, thereby providing an augmented construct. This should allow earlier return to full weightbearing and faster restoration of ankle and foot function without increasing the risk for secondary displacement of the fractured joint surfaces.

In a biomechanical study, Thorardson et al compared intraarticular calcaneal fractures fixed with standard internal fixation with those in which the osseous defect was filled with bone graft or SRS. In the specimens treated with the combination of hardware and SRS cement, cyclic loading produced significantly less deformation.

In a prospective clinical series, calcaneal fractures with joint depression were treated with a combination of internal fixation and SRS. Through the series, progressively shorter times to full weightbearing were prescribed. The last patients were allowed full weightbearing 3 weeks after surgery and showed no radiological evidence of loss of reduction.

 

Hip Fractures

The aim of hip fracture surgery is to produce fracture stability that will allow unrestricted weightbearing directly after surgery. This is because most patients who experience a hip fracture are elderly and have limited strength in their upper extremities that makes it difficult for them to reduce the weight carried by the injured hip. Unfortunately, the bone often is weakened by osteoporosis, which hampers the ability to achieve stability. In addition, necrosis, nonunion, and complications after internal fixation of displaced femoral neck fractures are frequent because of disturbed blood circulation to the femoral head. As a result, primary prosthetic replacement often is the treatment of choice.
However, even though deficient blood flow is the primary cause of complications, there are reports indicating that good primary stability can improve outcomes after internal fixation. Stankewich et al studied the use of calcium phosphate cement to augment comminuted femoral neck fractures fixed with cannulated screws. Under cyclic loading, the augmented specimens were significantly stiffer than specimens fixed with screws alone, and they failed at higher loads. Additional evidence comes from a prospective, randomized clinical study, in which patients with displaced femoral neck fractures were allocated to treatment with closed reduction and internal fixation with two cannulated screws either alone or in combination with SRS augmentation. The cement was used to augment the bone around the screw threads to enhance the holding characteristics in the femoral head and to fill the fracture void. The patients were examined with radiostereometric analysis, a radiologic technique that allows three-dimensional description of movement with a high accuracy. The radiostereometric analysis showed significantly better stability in the cement-augmented fractures with less overall movement, less distal migration of the femoral head fragment, and less varus angulation during early rehabilitation, although there were no significant differences between the groups at 6 and 12 months. There was no significant difference between the reoperation rates during the 12-month follow up.

Trochanteric fractures, which are almost as common as femoral neck fractures, rarely present any healing difficulties. The main concerns instead are related to mechanical problems when attempting to achieve stability. Two-part fractures seldom present any problems, but multifragmentary fractures, especially those without posteromedial support, often are technical challenges. In two biomechanical studies, trochanteric fractures with a detached minor trochanter were created and fixed with a sliding screw device alone or in combination with SRS to fill the posteromedial defect. Cyclic loading revealed that the specimens augmented with cement had significantly higher stiffness, stability, and strength, and less shortening at the fracture site. In addition, the strain on the medial bone surface in the augmented specimens was closer to normal than the strain in the specimens fixed with the metal device alone.

In another prospective, randomized clinical trial, patients with a trochanteric fracture that included a detached posteromedial fragment were treated with surgical fixation using a conventional sliding screw system alone or in combination with SRS. The purpose of augmentation was to restore a mechanically competent posteromedial arch that enabled a more efficient transfer of load between fracture ends while reducing the risk for secondary fracture displacement and cutting out of the lag screw. Radiostereometric analysis was used to measure fracture movement until 6 months after surgery, when all fractures were healed. The fractures augmented with cement were significantly more stable at all times, with reduced overall movement, less distal displacement, and less varus angulation when compared with fractures fixed with the metal device alone.

 

Spine

Injection of polymethylmethacrylate cement into the vertebral body has shown some promise for pain relief and possibly strengthening of osteoporotic vertebral bodies.

Early preclinical studies suggest that bioactive cements of either calcium phosphate or bioglass composition may be useful for vertebroplasty procedures.

 

Advantages and limitations of bioactive cements in fractures

The preclinical and biomechanical studies are promising, but clinical experience with bioactive cements thus far is based on only a few studies in a few clinical indications.

Although the gains in stiffness and strength are clear, additional work should be done to ensure that the cement does not have any detrimental effect on the healing process.

One potential drawback of SRS augmentation is shown by the radiostereometric analysis on hip fractures, which confirmed that SRS enhances stability for trochanteric fractures throughout the healing period, but in femoral neck fractures, showed enhanced stability only for the first weeks after surgery. The lack of difference in stability at later times for femoral neck fractures might imply fatigue of the calcium phosphate when used in this location, or it might be caused by biologic events stemming from circulatory disturbances at the fracture site.

Another potential drawback of the calcium phosphate cements is that they have very low strength in shear and tension, despite compressive strength intermediate between that of cancellous and cortical bone.

For example, the clinical studies on tibial plateau and calcaneus fractures suggest that SRS augmentation is beneficial in these indications, probably because the cement is subjected to relatively uniform compressive loading. In other locations, such as the hip, the loading conditions are complicated by shear and tension, suggesting that in the hip the cement would have to be supported with metal implants.

An important advantage of a calcium phosphate cement is that it reduces the need for bone graft and thereby eliminates donor site morbidity.

Bioactive cements will not replace the use of conventional metal implants but probably will influence the design of metal devices and the way in which they are used.

Until cements with adequate shear strength are available, most complex fractures that can be repaired with cement also will require metal supports.

On the basis of biomechanical studies and the limited clinical experience, it seems that the material can replace the use of cancellous bone graft for filling voids in compromised cancellous bone in some types of fractures.

It will not replace bone graft when there is a need for a material with osteogenic or osteoinductive properties, or when cortical bone graft contributes mechanical stability to a construct.

It is anticipated that the use of cements will enable faster and more aggressive rehabilitation, as the strength of the cement makes it possible to allow full weightbearing earlier than when bone graft is used.

 

References

 

Larsson S, Bauer TW; Use of injectable calcium phosphate cement for fracture fixation: a review; Clin Orthop Relat Res. 2002 Feb;(395):23-32.
 

Page created by: Lee Van Rensburg

Last updated 11/09/2015