Periprosthetic Osteolysis and Aseptic Loosening of Prostheses in Total Joint Arthroplasty

Total joint arthroplasty of the hip and knee has become one of the most frequent and rewarding operations in orthopedic surgery. World-wide more than one mil- lion such prostheses are implanted annually. With the steady rise in life expectancy long term complications related to implant loosening and periprosthetic fractures are on the rise. Efforts to sustain and improve the clinical survival of total joint implants has thus generated great interest.

Pathogenesis

Stability of the prosthesis within the surrounding bone is the decisive factor for flawless functioning and longevity of the implants. Osteolysis is a multifactorial process stemming from host, prosthesis, and surgical factors. Billions of wear particles are generated at material interfaces and are dispersed along the effec- tive joint space, into bone and the adjacent soft tissue, inducing an inflamma- tory reaction that leads to osteoclast activation and finally causing osteolysis. Over time without proper treatment osteolysis may progress to aseptic loosening and fail- ure of the implant. Initially most patients may have no clinical symptoms despite radiographic evidence of osteolysis or bone loss. Usually patients only become symptomatic when implant loosening (Fig. 20.1), implant failure or periprosthetic fractures occurs.

The main factors involved in periprosthetic osteolysis and aseptic loosening following total joint arthroplasty are:

▶ Wear-debris-induced osteolysis. Integration of the implant into the surrounding bone can be hindered by an inflammatory reaction (“foreign body reaction”) induced by macrophages absorbing small particles, mainly polyethylene and metallic wear debris, leading to activation of RANKL and OPG which then trigger osteoclastic activity. Another important factor is the inhibition of os- teoblast function mediated by wear particles. Finally osteolysis and bone loss around the implant occurs.

▶ Micromovement between surfaces: Implants that do not achieve adequate initial fixation will exhibit micromotion in response to load. The greater the area of friction the more osteoclasts are activated causing osteolysis around the implant which leads to fatigue failure at interfaces. When the distance between bone CHAPTER 20 Periprosthetic Osteolysis

and Aseptic Loosening of Prostheses

in Total Joint Arthroplasty

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and implant exceeds 150 µm connective tissue membranes are formed between implant and bone as well as between implant and cement. These membranes hinder the osteo-integration of the prosthesis. Many biochemical mediators are involved: cytokines, prostaglandins, metalloproteases and collagenases.

▶ Inappropriate mechanical load and stress shielding: Insertion of an implant leads to new biomechanical relationships between various regions of the surround- ing bone and the implant. Bone regions around the implant receiving high loads of stress result in bone apposition and higher bone density, whereas bone regions receiving lower stress loading react with bone loss (“stress shielding”

according to Wolffs’ law). Appropriate load transmission is an essential factor in maintaining bone volume. Optimal load transfer is influenced by implant design and stiffness of the implant. Bone loss around the implant due to stress shielding can account for up to 50% of the former bone stock in underloaded regions, which has been demonstrated by DXA measurements (Fig. 20.2). Fi- nally periprosthetic fractures can occur.

▶ Postoperative immobilization: The post-operative decrease in weight-bearing re- sults in local immobilization osteoporosis. Overall the postoperative bone loss mainly occurs in the first 6 months and can reach up to 50% of the former bone stock.

▶ Operative trauma: Thermic and mechanical necrosis caused by the surgical procedure and cementing techniques alter bone quality.

Diagnosis

Slight loosening of the implant remains symptomless for long periods. Significant loosening causes considerable pain on weight-bearing and on sudden movements, eventually resulting in a feeling of complete instability. Pain on rotation of the leg in a patient with a hip implant indicates loosening of the shaft and pain on axial compression may indicate loosening of the cup. Radiolucent lines more than 2 mm wide indicate loosening (Fig. 20.3), but localised and limited osteoly- sis, and incomplete radiolucent lines per se do not constitute evidence of loosen- ing of the implant. Migration of the prosthesis over time is diagnostic: migration of >5 mm indicates loosening. Implant migration indicates local bone loss which is a great problem in revision surgery. Besides standard radiographs (Fig. 20.4) also bone scans are useful to detect regions of high bone turnover around implants, and computed tomography to quantify the amount of bone loss.



Fig. 20.1 Periprosthetic osteolysis caused by activated osteoclasts at the bone-implant in- terface

Diagnosis

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Treatment Strategies

Causative therapy consists of replacing the prosthesis. Indications for this are pain, functional limitations and migration of the implant. Accompanying osteoporosis and loss of bone stock around the implant can turn this operation into a more dangerous and more difficult one than the index operation. However recent ad- vances in technology and in materials for cementing may improve long-term re- sults in the future. Intensive research is underway to improve the survival of the implants including local application of bisphosphonates and implant coating with osteoinductive factors. Implantation of cementless implants is recommended for younger patients with bone of good quality, as less bone is removed, which en- sures a more favorable situation if a revision procedure has to be made later.

Various modifications to improve osteointegration of implants are under inves- tigation:

Fig. 20.2 DXA measure-

ment of bone mineral

density in periprosthetic

region: division into 7

zones according to Gruen

(Lunar Prodigy)

169

▶ Optimization of prosthetic design with optimal load transfer to the bone

▶ Better cementing techniques

▶ Local application of growth factors (Hydroxylapatite, TGF-β, BMP2) as well as PTH to improve osteo-integration of the implant

Bisphosphonates

Early administration of nitrogen-containing bisphosphonates inhibits peri-implant osteoclastic resorption. This has been demonstrated in numerous animal experi- ments which showed a decrease in bone loss around the implant. Current clinical studies are hampered by short follow ups. A recently published meta-analysis of 6 randomised controlled studies showed that bisphosphonates given in the immedi- ate post-operative period prevented periprosthetic bone loss and resulted in a higher

Fig. 20.3 Peri-implant bone resorption (“linear osteolysis”) at the interface of the acetabular component, “radiolucent lines”

Bisphosphonates

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periprosthetic bone mineral density at the end of the study period compared to con- trols.

In cases where total joint arthroplasty is planned, therapy with bisphosphonates can be given in the following situations:

▶ Underlying systemic or local osteoporosis: a higher bone density in the periop- erative period may reduce the postoperative bone loss and extent of peripros- thetic osteolysis.

▶ Underlying chronic inflammatory joint disorder: Inhibition of osteoclasts and suppression of osteoclast activating mediators, as well as an increase in bone

Fig. 20.4 Peri-implant bone resorption at

the interface of the femoral (“geographic

osteolysis”) and acetabular component

(“linear osteolysis”)

171

density can help to reduce postoperative bone loss and to increase the time of implant survival.

The following treatment protocols are recommended. Dosages and time intervals depend on the type and severity of the underlying condition:

▶ Alendronate (Fosamax ® ⁾ 70 mg orally once weekly

▶ Risedronate (Actonel ® ⁾ 35 mg orally once weekly

▶ Pamidronate (Aredia ® ⁾ 30–60 mg intravenously every 3 months

▶ Ibandronate (Bonviva ® ⁾ 3 mg intravenously every 3 months

▶ Ibandronate (Bonviva ® ⁾ 150 mg orally monthly

▶ Zoledronate (Aclasta ® ⁾ 5 mg intravenously annually The following parameters are used to monitor therapy:

▶ Clinical examination

▶ Control radiographs

▶ DXA (bone densitometry)

▶ Markers of bone remodelling

To establish the efficacy of bisphosphonates in preventing bone loss after total joint arthroplasty more randomised clinical trials with large numbers of patients, long term follow up and clinically relevant endpoints (functional outcomes, revi- sion rates) have to be conducted. However the current results for prevention of periprosthetic bone loss with bisphosphonates are very promising.

Bisphosphonates