INTRODUCTION

Hip arthroplasty is one of the most successful of all orthopedic operations,but the results do deteriorate with time due to loosening.In the 1970s,the hypothesis of wear-particle-induced loosening,later called particle disease,was proposed: It was assumed that wear particles cause a foreign-body response leading to periprosthetic osteolysis and ultimately to late prosthetic loosening.Wear particles are still widely considered to be the main cause of loosening[1-4].However,there is much evidence that loosening is already initiated during or shortly after surgery (due to insufficient initial fixation or resorption of a necrotic bone bed) and that the prosthetic micromovements then cause devitalizing periprosthetic fluid pressure fluctuations leading to periprosthetic osteolysis[5-9].This commentary focuses on the causal relationship between prosthetic loosening and periprosthetic osteolysis.

WEAR PARTICLES PER SE DO NOT INDUCE OSTEOLYSIS

The hypothesis of wear-particle-induced loosening presupposes that wear particles are somehow transported into the interface between bone and prosthesis and once there,trigger a foreign-body response leading to periprosthetic osteolysis (and ultimately to prosthetic loosening).However,histological studies indicate that a stable implant has a biological barrier that prevents wear particles from entering into the bone-prosthetic interface[10,11].Even if the biological barrier were defective,experiments have shown thatparticles (if very gently deposited between the bone surface and a stable implant) do not induce osteolysis[12,13].Thus,wear particlesappear not to induce osteolysis.

ENDOTOXINS AND DAMPS CAN INDUCE OSTEOLYSIS

Wear particles contaminated by endotoxins can induce transient osteolysis[14,15],but it has been experimentally shown that endotoxins are rapidly eliminated or inactivated[13].By contrast,prosthetic micromovements ofprosthetic components can cause sustained,devitalizing spikes of high fluid pressure in the bone-implant interface,which can lead to progressive periprosthetic osteolysis[5-9].The molecular mechanism appears to be that necrotic osteocytes release DAMPs (damage-associated molecular patterns,danger signals,or alarmins)[16],which,a unique pattern recognition receptor,reinforce osteoclastogenesis[17].DAMPs,released due to prosthetic loosening,may,therefore,(unlike endotoxins) induce sustained excessive osteoclast activity and thus cause progressive periprosthetic osteolysis.

DAMPS-COATED PARTICLES CAN INHIBIT BONE INGROWTH

A series of animal experiments with polyethylene particles inserted into the interface between the bone and a movable part of a previously installed implant have shown inhibition of bone ingrowth only when combined with movements at the interface,no inhibition occurred at a stable interface.Remarkably,after the movements ceased,the inhibition of bone ingrowth persisted if particles were present,while no inhibition occurred in the control group without particles[12].

A plausible explanation of the persistent inhibition of bone ingrowth after the movements ceased is that the movements caused the release of DAMPs,that adhered to the polyethylene particles at the interface,thus forming DAMPs-coated bone-formation-inhibiting polyethylene particles.Varying degrees of DAMPs-coating may actually explain why different authors have come to very different conclusions about the importance of the material and size of the wear particles in loosening (a significant foreign-body response to particles of cement,metal,and polyethylene have been reported,but also no or almost no response)[18].A similar mechanism (DAMPs-coated particles) for osteolysis may also apply to experimental models exposed to both surgical trauma and wear particles.

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UNCEMENTED PROSTHETIC COMPONENTS DO NOT FORM DAMPS-COATED CEMENT PARTICLES

Radiostereometric analysis (RSA) enables highly accuratemeasurements of the prosthetic component migration after surgery.Many RSA studies of hip prostheses have shown that early migration poses a risk of future failure—the larger the early migration,the greater the risk of future failure[19-24].However,some RSA studies indicate that certain uncemented femoral components appear to achieve stability and possibly even osseointegration during the healing period despite significant early migration[25-27].

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If,as suggested in these studies,these uncemented femoral components (unlike cemented femoral components with similar significant early migration) really become osseointegrated during the healing period,a probable explanation is that no DAMPs-coated cement particles,which could inhibit bone ingrowth and thereby prevent osseointegration,have been formed.

Mj?berg B wrote this review.

CONCLUSION

The recent clarification of the molecular mechanism behind osteoclastogenesis (the pattern recognition receptor to osteocyte-derived DAMPs)[17] allows us to better understand the causal relationship between prosthetic loosening and periprosthetic osteolysis: Loosening is initiated during or shortly after surgery (due to insufficient initial fixation or resorption of a necrotic bone bed).The micromovements of thus loosened prosthetic components may,periprosthetic fluid pressure fluctuations,cause necrotic osteocytes,which release DAMPs that reinforce the osteoclast activity and lead to periprosthetic osteolysis.Later and,DAMPs-coated wear particles may be formed,which,by inhibiting bone ingrowth,may affect the progression of loosening.

Sweden

They had been put to bed early, with every one a crown of gold upon her head. There was in the same chamber40 a bed of the like bigness, and it was into this bed the Ogre s wife put the seven little boys, after which she went to bed to her husband.

So he changed himself to a horse, such a fine horse, too, that his father got a high price for it at the market; but after the bargain was made, and the money paid, the boy changed again to his own shape, when no one was looking, and went home

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers.It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license,which permits others to distribute,remix,adapt,build upon this work non-commercially,and license their derivative works on different terms,provided the original work is properly cited and the use is noncommercial.See: https://creativecommons.org/Licenses/by-nc/4.0/

All authors declare that there is no any conflict of interest.

Bengt Mj?berg 0000-0002-2887-4194.

Swedish Orthopaedic Association; Nordic Orthopaedic Federation; European Federation of National Associations of Orthopaedics and Traumatology.

Wang LL

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Wang LL