for decades , joint replacement has been a procedure with major impact on the quality of life in elderly patients with joint degenerative diseases or traumatic injuries .
unfortunately , some patients develop symptoms after surgical intervention . in the majority of patients , aseptic loosening due to biochemical reaction of the bone
both entities have a very similar clinical appearance , but require different therapeutic approaches due to different pathophysiological substrates ( 1 ) .
lack of a single imaging modality that could clearly differentiate between infections and loosening makes this problem a challenge in the routine workup of these patients .
laboratory analysis , including white blood cell count , erythrocyte sedimentation rate ( esr ) and c - reactive protein ( crp ) are not specific enough .
canner et al . found that out of fifty - two patients who had an infection following joint arthroplasty , only eight ( 15% ) had leukocytosis ( 2 ) .
the esr may remain elevated for months after an uncomplicated total hip replacement ( 3 ) .
crp levels increase in a non - specific manner as a result of infectious , inflammatory or neoplastic disorders .
conventional imaging methods are helpful in some situations when complications arise ( 4 , 5 ) , but their diagnostic potential in distinguishing loosening and inflammation are limited .
ct is superior to radiography in imaging soft tissue abscesses ( 6 ) ; however , not a recommended diagnostic tool due to significant artifacts on the images at the location of the prosthesis that hamper the optimal interpretation of the results .
thus , non - attenuation - corrected images must be interpreted to avoid false - positive results if pet / ct is used for the evaluation of painful prosthesis ( 7 ) .
aspiration biopsy of the joint was regarded as a gold standard , but it is not convenient for the patient and may not always be helpful in distinguishing the two above - mentioned pathological entities . a positive result can confirm infection , but a negative result can not exclude it ( 8) .
nuclear medicine modalities offer several diagnostic methods that are dedicated to the diagnosis of infection and are not affected by orthopedic implants .
three - phase bone scintigraphy ( tpbs ) is widely accepted for the diagnosis of different pathological processes of the musculoskeletal system including detection of infection with a high sensitivity and limited specificity in the diagnosis of infected joint prostheses ( 9 ) .
it is noticeable that reported results of different studies dealing with the problem of painful joint prosthesis show variation , which is mostly due to different interpretation criteria applied ( 10 , 11 ) .
tpbs , with an accuracy of about 50 - 70% can be performed as the modality of primary choice in these patients , but it should be combined with other diagnostic modalities ( 12 ) .
white blood cell ( wbc ) scintigraphy labeled with 99mtc hmpao or 111in - oxine or anti - granulocyte scintigraphy using 99mtc - labeled monoclonal antibodies ( moab ) or their fragments are frequently used nuclear medicine imaging modalities in the detection of infection and inflammation , but it is important to emphasize that neither of these imaging methods can reliably differentiate sterile inflammation from infection ( 13 ) .
significant decrease in the accuracy of wbc imaging is caused by the fact that labeled leukocytes are accumulating both in infected tissue and in bone marrow ( 10 ) . a combined study consisting of wbc imaging and complementary bone marrow ( bm ) imaging performed with radiolabeled sulphur colloid
is based on the fact that both radiopharmaceuticals accumulate in marrow ; whereas , wbcs accumulate in infection , but sulfur colloid does not .
although the combination of these two modalities increases the accuracy in the diagnosis of osteomyelitis up to 90% , pitfalls that could affect the results are not negligible ( 14 ) .
18f - fdg - pet is a promising imaging modality for the evaluation of a variety of infectious and inflammatory processes ( 15 ) .
in addition , there are reports indicating that in the evaluation of inflammation or infection , 18f - fdg - pet is even more accurate than conventional nuclear medicine procedures ( 16 ) . these features of 18f - fdg - pet diagnostic modalities encouraged many professionals to perform research on its applicability in patients with painful prostheses .
however , the results of the studies dealing with the role of 18f - fdg - pet are so far rather inconclusive and need to be more clearly defined ( 12 ) . according to chacko et al . , the intensity of uptake is not useful for separating the infected from the aseptically loosened device ( 17 ) .
the periprosthetic glucose metabolism could also be enhanced to certain degrees in normal cases , which have been addressed in another study ( 18 ) , and could hamper the interpretation of the examination .
the reason for this shortcoming is to our opinion the unawareness of physiological remodelling processes that could be seen in asymptomatic patients .
the aim of this study was to demonstrate this  physiological  pattern and discuss the findings in the literature .
in the present study , we aim to delineate different metabolic patterns in asymptomatic patients with hip prostheses and to improve the specificity of 18f - fdg - pet in patients with suspected septic loosening of hip prosthesis .
twelve patients , ( 6 males , 6 females ) ; mean age , 73  7 ( range , 58 - 91 ) years were enrolled prospectively into the study .
none of the patients expressed any symptoms in regard to their implanted prosthesis and none of them had hematological malignancies or any metabolic bone manifestation of the primary tumor .
the pet studies were performed on a full ring pet - scanner ( siemens exact , knoxville , usa ) as described in earlier studies ( 19 ) .
the results are summarized in table 1 . with findings related to periprosthetic enhanced uptake ,
figure 1 demonstrates a case of a patient with asymptomatic hip prosthesis on both sides with enhanced uptake in the left neck region .
t = trochanter , n = neck , m = male , f = female , l = left , r = right
one of the largest samples of patients with hip prosthesis examined with 18f - fdg - pet was reported by reinartz and colleagues who compared pet with tpbs .
the authors concluded that 18f - fdg - pet is a highly accurate diagnostic procedure to differentiate reliably between aseptic loosening and periprosthetic infection ( 18 ) .
they described , by a qualitative analysis , the different patterns of periprosthetic 18f - fdg uptake in different conditions , from normal to septic loosening 6 months after arthroplasty .
18f - fdg - pet has great potential in detecting the infection , but in cases of increased aseptic loosening , periprosthetic uptake of 18f - fdg could be caused by wear - induced polyethylene particles and the subsequent growth of aggressive granulomatous tissue ( 16 ) .
non - infectious inflammatory reactions around the neck of the prosthesis are common findings months or even years after surgery and they should not be interpreted as a finding suggestive of infection ( 21 ) .
application of suv ( standard uptake value ) as a semiquantitative parameter is usually a very important tool in the interpretation of oncological pet images , but it can not be applied as a reliable criterion in inflammatory pathology due to low specificity , particularly not as a single criterion ( 10 ) . knowing the limitations of 18f - fdg - pet alone and taking into account the mechanism of its uptake in malignant tissues , leukocytes were labeled with 18f - fdg in order to increase its affinity to the inflamed tissue .
although the first results were promising , it was found that 18f - fdg was rapidly released from the leukocytes .
it has been suggested that the amount of increased 18f - fdg uptake is less important than the location of increased 18f - fdg uptake when this technique is used to diagnose periprosthetic infection in patients who had undergone prior hip arthroplasty ( 16 ) .
uptake pattern seems to be of essential importance in the diagnosis of infection and is defined as very suggestive of infection if the 18f - fdg uptake between the bone and prosthesis at the level of the midshaft portion of the prosthesis is present ( 23 , 24 ) .
this suggests that more standardized criteria for the interpretation of the 18f - fdg scan for the diagnosis of infection on the prosthesis placement should be defined and applied in practice .
depending on the type of prosthesis and on other factors , hip prosthesis can show different metabolic patterns . keeping in mind different metabolic patterns of periprosthetic 18f - fdg uptake in different conditions and the reliability of periprosthetic suv - measurement with the new pet / ct devices
, it seems to be of the utmost importance to find visual criteria that could be applied in these cases ( 18 ) . in this study
, we could demonstrate ( table 1 ) this pattern of hypermetabolic areas that could be defined more likely as normal and not caused by septic or aseptic loosening only on the neck and/or trochanteric area .
two patients who showed enhanced periprosthetic uptake in two regions , had a history of re - implantation in one case and a period longer than 10 years after the surgery in the second case .
interestingly , we could not observe focal enhanced glucose metabolism in the stem or tip region in any patient .
these findings are also of importance to rule out a suspected infection , as it was shown in a recent study where fdg - pet had a sensitivity of 100% and a negative predictive value of 100% ( 25 ) .
the study is limited by the fact that the patients could not provide information regarding the type of prosthesis , particularly whether they were cemented or not .
no patient had a leukocytosis , but 8/12 patients -- with or without periprosthetic - enhanced uptake -- had an elevated crp . since they were all referred for oncological reasons , data was not taken into consideration .
the results of this study demonstrate a non - specific pattern of enhanced 18f - fdg - uptake in asymptomatic patients in the neck or trochanteric region after arthroplasty , which should be taken into consideration for correct interpretation of metabolic studies in patients with suspected septic loosening of the hip prosthesis .
 background : joint replacement is a procedure with a major impact on the quality of life of patients with joint degenerative disease or traumatic injuries . 
 however , some patients develop symptoms after the intervention caused by mechanical loosening or infection . 
 metabolic imaging by 18f - fdg - pet investigated in these patients isoften hampered by low specificity for diagnosis of possible septic vs. mechanical loosening . 
 the reason for this shortcoming is to our opinion the unawareness of physiological remodeling processes that could be seen in asymptomatic patients.objectives:in order to overcome this drawback , we aimed to find out the physiological metabolic functional pattern in asymptomatic patients with implanted hip prosthesispatients and methods : twelve patients ( 6 males , 6 females ) ; mean age 73  7 ( range 58 - 91 ) years were prospectively enrolled in the study . 
 the patients were admitted to our department for oncological referral with implanted hip prostheses . 
 all patients explained no symptoms with regard to their implanted prosthesis . 
 the attenuation corrected images were used for analysis.results:fourteen hip prostheses in 12 patients were visually analyzed . 
 seven out of 14 prostheses among 12 patients showed focal periprosthetic enhanced metabolism , two of which showed two sites of enhanced uptake ; whereas , the remaining five prostheses showed singular hypermetabolic areas within the periprosthetic site . 
 the remaining seven prostheses in the other five patients showed no periprosthetic - enhanced uptake.conclusion:of the asymptomatic patients investigated , 58% showed focal enhanced periprosthetic glucose metabolism . 
 this finding should be taken into consideration as a more probable unspecific metabolic pattern for correct interpretation of 18f - fdg - pet studies in patients with suspected septic loosening of the hip prosthesis . 
1. Background
2. Objectives
3. Patients and Methods
4. Results
5. Discussion