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 .