THE DIAGNOSIS OF EPICONDYLITIS is mainly based on

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1 2180 ORIGINAL ARTICLE Three-Phase Bone Scintigraphy in Chronic Epicondylitis Tuomo T. Pienimäki, MD, PhD, Reijo J. Takalo, MD, PhD, Aapo K. Ahonen, MD, PhD, Jaro I. Karppinen, MD, PhD ABSTRACT. Pienimäki TT, Takalo RJ, Ahonen AK, Karppinen JI. Three-phase bone scintigraphy in chronic epicondylitis. Arch Phys Med Rehabil 2008;89: Objective: To assess the utility of 3-phase bone scintigraphy as a complementary diagnostic method in chronic epicondylitis. Design: A cross-sectional study. Setting: Hospital outpatient clinic admitting patients with musculoskeletal disorders. Participants: Patients (N 59; 68% women) with unilateral chronic epicondylitis. Interventions: Not applicable. Main Outcome Measures: Three-phase bone scintigraphy was performed after an intravenous injection of 550MBq 99m technetium-labeled hydroxymethyline diphosphonate ( 99m Tc-HDP) in the patients. Blood flow and blood pool phases were graded visually as normative or abnormal. In the bone metabolic phase, the scintigraphic radiograph images were evaluated using a transmission densitometer. The ratio between maximal bone uptake of 99m Tc-HDP in each epicondyle and the mean of that in the adjacent humerus was used as a bone uptake measure, which was compared with clinical data (pain questionnaire, pain drawing, cubital pain thresholds, muscle strength) and with work ability and lifestyle factors. Results: The bone uptake of 99m Tc-HDP of the affected epicondyle was 33% and 17% higher in men and women, respectively, compared with the corresponding healthy epicondyle (P.001 and P.007). High bone uptake of 99m Tc-HDP was associated with better work ability, grip strength, and muscle performance in both sexes but was not correlated with the pain measures. Blood flow phases had a positive correlation with the duration of symptoms and a negative correlation with the bone uptake of 99m Tc-HDP, grip strength, and work ability. Conclusions: High bone uptake of 99m Tc-HDP among patients with chronic epicondylitis was associated with better muscle strength, work ability, and arm function. In chronic cases, a higher degree of bone uptake of 99m Tc-HDP may thus indicate a healing response in the bone tissue. Key Words: Bone and bones; Rehabilitation by the American Congress of Rehabilitation Medi- THE DIAGNOSIS OF EPICONDYLITIS is mainly based on history and clinical examination. With the exception of MRI, 1 conventional radiography and other imaging modalities provide minimal diagnostic and classification information regarding this disorder. MRI has shown local ruptures or swelling in the origin of the common extensor or flexor tendon. 2,3 In the diagnosis of upper-extremity repetitive strain injuries, 3-phase bone scintigraphy has shown low sensitivity and accuracy. 4 However, epicondylitis is a local pathologic condition, and the possible involvement of the underlying bone in the elbow has been poorly studied in this overuse injury. From this point of view, 3-phase bone scintigraphy is a potential imaging modality. So far, associations between bone scintigraphy findings and subjective pain and clinical findings have remained unstudied. Bone scintigraphy may provide clinically relevant information regarding the natural course of epicondylitis. Bone scintigraphy is a very sensitive method for detecting focal bone disorders, such as primary tumors, metastases, fractures, infections, and enthesopathies. The focally increased bone uptake of 99m Tc-HDP in bone scintigraphy most often reflects the osteoblastic response of bone to a local injury irrespective of the actual etiology; for example, it is a regenerative process. 5 The aim of the present study was to assess the usefulness of 3-phase bone scintigraphy as a complementary diagnostic method in a group of patients with chronic epicondylitis, and to compare the results with clinical data. METHODS Patients The study group consisted of 59 patients (table 1) with chronic unilateral epicondylitis, referred to Oulu University Hospital because of failure of traditional conservative measures. Before inclusion, 22 patients had received cast immobilization, 41 oral medications, 27 topical medications, and 24 passive local physical treatment, while 53 patients had received local steroid injections. The study was approved by the Ethics Committee of Oulu University Hospital. Informed consent was obtained before the study. Clinical Examination and Manual Tests The patients were interviewed and examined by an experi- physician (T.T.P.) before all measurements. In the intercine and the American Academy of Physical Medicine andenced Rehabilitation view, the history of the disorder, duration of symptoms, number of local injections, number of days on sick leave, other treatments, leisure time physical activity, and smoking habits were obtained. The clinical examination included assessment of the patient s general physical status, collection of anthropometric data, a brief From the Finnish Institute of Occupational Health, Oulu (Pienimäki, Karppinen); Department of Radiology, Division of Nuclear Medicine (Takalo) and Department of Physical Medicine and Rehabilitation (Karppinen), Oulu University Hospital, Oulu; Department of Clinical Physiology and Nuclear Medicine, HUSLAB/Helsinki University Hospital, Helsinki (Ahonen), Finland. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated. Reprint requests to Tuomo Pienimäki, MD, PhD, Finnish Institute of Occupational Health, Aapistie 1, Oulu, FI-90220, Finland, tuomo.pienimaki@ttl.fi /08/ $34.00/0 doi: /j.apmr GS MRI 99m Tc-HDP VAS List of Abbreviations grip strength magnetic resonance imaging 99m technetium-labeled hydroxymethyline diphosphonate visual analog scale

2 BONE SCINTIGRAPHY AND EPICONDYLITIS, Pienimäki 2181 Table 1: Patient Characteristics Character Women Men Total Number of patients Age (y) 45 (34 58) 46 (36 61) 45 (34 61) Height (cm) 163 ( ) 175 ( ) 167 ( ) Weight (kg) 65 (47 92) 79 (65 98) 70 (47 98) Dominant vs nondominant arm affected 33/7 14/5 47/12 Lateral vs medial syndrome 35/5 17/2 52/7 Duration of symptoms (wk) 45 (16 122) 45 (18 116) 45 (16 122) NOTE. Values are mean (range) unless otherwise noted. neurologic examination, and a general musculoskeletal examination with special attention to the upper extremities. The examination and measurements (described in further detail below) also included manual tests, 6 a 7-item pain and disability questionnaire using a VAS, 7,8 a whole-body pain drawing, 8 pressure pain thresholds of the cubital regions, 8,9 isometric grip strength measurements, 10 and isokinetic performance measurements of wrist flexion and extension and forearm pronation and supination. 11 Manual tests. The tests included (1) palpation for tenderness above the lateral or medial epicondyle; (2) resisted wrist extension test and resisted wrist flexion test for lateral and medial epicondylitis, respectively; (3) resisted middle finger extension test; and (4) Mill s test, which involves the production of lateral epicondylar pain with passive elbow extension, forearm pronation, and wrist flexion. 6 The resisted wrist extension test or resisted finger extension test were considered positive if they provoked epicondylar pain at the origin of the extensor carpi radialis brevis tendon (resisted wrist extension test) or at the origin of the flexor carpi ulnaris tendon (resisted finger extension test) at the lateral or medial humeral epicondyle. 6 Pain Questionnaire A pain questionnaire with 7 questions on pain and disability was used to register current perceived pain and disability during the previous week. 7,8 The questions addressed the following topics: pain at rest, pain under strain, relief of used medication, subjective disability to work, disability to lift objects of 2kg or more with the hand, disability in leisure time (hobby) activities, and sleep disturbance. The patients answered each question on a 10-cm nonsegmented VAS from 0 (no pain or disability) to 10 (worst imaginable pain or disability). The patients were advised to answer the pain questionnaire in the beginning of the examination session. The sum of all 7 pain questionnaire scores was calculated and used as an additional total pain score measure in the analysis. Pain Drawing A whole-body pain drawing 7 was used to categorize the subjects into 4 groups according to the location and extension of pain (0 no pain; 1 local elbow pain; 2 elbow, forearm, and hand pain; 3 more widespread pain). Pain Thresholds PPTs were measured bilaterally with a dolorimeter a over the lateral and medial epicondyles and over the arcade of Frohse (radial tunnel). The measurement protocol included 2 measurements at each testing point, of which the mean was calculated. 8 Grip Strength Isometric grip strength was measured with a computerized dynamometer. b The measurements were taken with a grip width of 2cm Three attempts were performed with the maximum (maximal GS) of all 3 grips recorded. The difference in maximal GS between the affected and the healthy arm was calculated, and the grip strength of the affected arm was expressed as a percentage of the healthy arm. Both the affected and the healthy arm were measured with exactly the same protocol. The patients were in a sitting position with the elbow 90 flexed and the forearm in a neutral position. Isokinetic Performance of the Arms The concentric isokinetic performance of upper-extremity wrist flexion and extension and forearm pronation and supination was tested using a computerized Lido Multi-Joint isokinetic dynamometer c with a fixed radial velocity of 90 /s. Five repetitions were performed. Both the affected and the healthy arm were measured with the same protocol, and the differences between the arms were registered. Of the results, peak torque (Nm), average peak torque (Nm), and the amount of work accomplished a repetition (J) were used for statistical analysis. 11 Diagnostic Inclusion and Exclusion Criteria The diagnosis of epicondylitis was based on history, clinical examination, and clinical manual tests. With 1 exception, the diagnostic inclusion criteria were the same as used in the studies by Haker and Lundeberg, 13 where 2 of the 4 tests should be positive, producing local epicondylar pain. In our study, 1 inclusion criterion was pain on palpation on the lateral or medial epicondyle. In addition, for lateral epicondylitis, we required that 2 of the 3 other manual tests had to be positive, while for medial epicondylitis, 1 test had to be positive to enable inclusion. Patients with a definite clinical lateral or medial epicondylitis were included in the study. The clinical exclusion criteria were other arm disorder or systemic disease affecting arm function, such as carpal tunnel disease, rheumatoid arthritis, cubital osteoarthritis, rotator cuff tendonitis, and complication after a fracture of the upper extremity. Fifty-nine patients met the inclusion criteria. Thirty-nine patients tested positive for all of the manual tests, 14 patients tested positive on 3 of the tests, and 6 tested positive on 2 of the tests. The patients represented typical chronic patients with epicondylitis and a poor response to traditional treatments. Bone Scintigraphy The 3-phase bone scintigraphy was performed after an intravenous injection of 550MBq 99m Tc-HDP. The elbows were imaged from the posterior view. The study included a blood flow phase (sequential images every 2s for 30s), a blood pool phase (4 6min postinjection), and a bone metabolic phase (3h postinjection). A low-energy general purpose collimator was used in the blood flow and blood pool phases. Bone metabolic images were obtained using an acquisition time of 10 minutes and a high-resolution collimator. Blood flow and blood pool images were evaluated visually and independently by 2 nuclear medicine physicians (R.J.T. and A.K.A.) unaware of the patient s clinical status. The phases were graded as normal (0) or abnormal (1) in each patient, with abnormal score signifying greater activity in the affected elbow than the contralateral elbow. In the bone metabolic phase, the uptake of 99m Tc-HDP was quantified from radiograph films using an X-Rite 331 B/W Transmission Densitometer. d From these values, the epicondyle to humerus ratio was computed for each epicondyle.

3 2182 BONE SCINTIGRAPHY AND EPICONDYLITIS, Pienimäki classes (1 low, 2 slight, 3 moderate, 4 high) according to the uptake intensity and adjusted for sex. Demographics, clinical examination findings, pain variables, muscle strength, and muscle performance of the affected arms were analyzed according to the classes using an independent samples t test for continuous or nonparametric tests for ordinal parameters. Spearman correlations were used in the analysis between clinical characteristics and blood pool results. SPSS software for Windows e was used in the analyses. Fig 1. The values of bone uptake of 99m Tc-HDP of the affected epicondyles compared with corresponding healthy epicondyles in men and women expressed from densitometry results as epicondyle to humerus ratios. Box plot presentation, paired t test. Statistical Analysis The ratios of bone uptake of 99m Tc-HDP (affected epicondyle to the ipsilateral humerus) were categorized into 4 RESULTS In men, the bone uptake of 99m Tc-HDP of the affected epicondyles was 33% higher than that of the corresponding healthy epicondyle (P.001). The uptake values of women were lower than those of men, and the corresponding difference compared with the corresponding healthy epicondyle was 17% (P.007) (fig 1). The pain scores in the pain questionnaire, the extent of pain in the pain drawing, and the duration of symptoms did not differ significantly between the classes of bone uptake of 99m Tc-HDP (table 2). The pressure pain thresholds of affected epicondyles did not differ significantly between the classes either (P.721) (see table 2), but the pressure thresholds of the arcade of Frohse in the affected arm were Table 2: Comparison of Demographic and Clinical Patient Data, Pain Questionnaire Items, Extent of Pain (Pain Drawing), Grip Strength, and Isokinetic Performance Results Among the 4 Classes of Bone Uptake of 99m Tc-HDP Character Measure Class of Bone Uptake of 99m Tc-HDP Low Slight Moderate High P* Sex Women/men 10/5 10/5 10/5 10/4 Hand dominance Dominant/nondominant 12/3 13/2 12/3 11/3.943 BMI kg/cm Symptoms duration wk Injections n Sick leave wk Physical activity Regular exercise (%) Hobby Upper extremity (%) Work ability Unable to work (%) Smokers (%) Workload Heavy (%) Perfusion Positive ranks (n) Blood pool Positive ranks (n) Pain questionnaire (VAS) Pain at rest (cm) Pain under strain (cm) Relief of medications (cm) Work disability (cm) Lifting (cm) Hobby limitations (cm) Sleep disturbance (cm) Total pain (VAS) Sum of 7 items (cm) Pain drawing Widespread pain (%) PPT of the affected epicondyle % of healthy epic PPT of the arcade of Frohse % of healthy side Grip strength Nm Isokinetic work Wrist flexion (J) Wrist extension (J) Supination (J) Pronation (J) NOTE. Values are mean SD unless otherwise noted. Abbreviation: BMI, body mass index. *One-way analysis of variance.

4 BONE SCINTIGRAPHY AND EPICONDYLITIS, Pienimäki 2183 Table 3: Significant Correlations Between Clinical Characteristics and Blood Flow (n 52) Measure Blood Flow (Perfusion) Correlation Coefficient P Duration of symptoms (wk) Work ability (yes/no) Number of injections Grip strength Class of bone uptake of 99m Tc-HDP Blood pool (0 2) NOTE. Correlations were analyzed using Spearman correlation coefficients. significantly higher in the higher classes than the lowest class (P.007) (see table 2). Blood flow (perfusion) images were classified abnormal for 7 (13%) of 52 patients, and blood pool analysis was abnormal for 12 (22%) of 54 patients. Five of the 7 positive blood flow images were in the lowest class (P.033) (see table 2), whereas the 12 positive blood pool images were more regularly distributed in the uptake classes (P.055) (see table 2). Table 3 shows that the blood flow rating was positively correlated with the duration of symptoms and grip strength and negatively with the uptake class (r.315; P.023) and reported work ability. Both blood flow and pool results were correlated negatively with the number of prior local steroid injections (see table 3). High bone uptake of 99m Tc-HDP was associated with significantly better reported work ability (P.032) (see table 2). The proportion of smokers, duration of symptoms, and body mass index values of the patients, and the distribution of high or low workload did not differ significantly between the classes (see table 2). Based on the clinical examination, the results of the manual tests did not show any association with the bone uptake of 99m Tc-HDP, blood pool, or blood flow classification. Maximal GS was significantly higher in higher classes than in the lowest one (fig 2). All isokinetic performance measures of the wrist and forearm were higher in higher classes than in the lowest one, but the differences were not statistically significant (see table 2). The results of peak torques and average peak torques showed a similar trend. DISCUSSION This study is the first to use 3-phase bony scintigraphy in chronic epicondylitis. The results indicate that high bone uptake of 99m Tc-HDP in chronic epicondylitis is associated with better muscle strength and better reported work ability. The differences in the bone uptake of 99m Tc-HDP did not associate with the results of manual tests or subjective pain measures. Moreover, low bone uptake of 99m Tc-HDP and high blood flow were associated with a greater reported functional loss of the arm. The patients of this study had chronic epicondylitis with poor response to traditional treatments. The patients were categorized into quartiles according to bone uptake intensity level and the results were adjusted for sex, because men had higher values in bone uptake of 99m Tc-HDP than women. After adjustment, the classes were comparable in both sexes. The present study also included 7 patients with medial epicondylitis with bone uptakes of 99m Tc-HDP comparable to those of the patients with lateral epicondylitis. In this study, high bone uptake of 99m Tc-HDP was associated with better function of the arm, better self-reported work ability, and less muscle tenderness. Therefore, high bone uptake of 99m Tc-HDP may reflect a healing process of epicondylitis. Our results are in accordance with the concept that focally increased bone uptake of 99m Tc-HDP in bone scintigraphy may reflect a regenerative process. 5 Abnormal blood flow and blood pool both reflect chronic prolonged inflammation. Increased blood flow was negatively correlated with the number of steroid injections. In a study by Smidt et al, 14 patients who were treated with corticosteroid injections had poorer recovery and more relapses than patients who received physiotherapy or were only observed. The present study did not show any correlation between the number of injections given, reported arm function, and the bone uptake of 99m Tc-HDP. Study Limitations The study has some practical limitations. A relatively small sample of chronic patients was analyzed, and lack of acute or subacute cases limits a wider generalization of the results to more acute stages of epicondylitis. The study design was cross-sectional; therefore, causal conclusions cannot be drawn. Three-phase bone scintigraphy has not been used previously in the evaluation of chronic epicondylitis; therefore, direct comparisons with other studies are not possible. CONCLUSIONS High bone uptake of 99m Tc-HDP may indicate a regenerative healing process of a focal overuse-type injury. Patients with high bone uptake of 99m Tc-HDP may have a better outcome than those with no or minimal bone uptake. Furthermore, the bone uptake of 99m Tc-HDP may enable subclassification of patients with epicondylitis, which could be of value in designing treatment interventions for this highly prevalent disorder. These preliminary results need to be replicated in other patient populations. Fig 2. Grip strength of the affected arms in different classes of bone uptake of 99m Tc-HDP expressed as percent values compared with the patients healthy arms. Box plot presentation, 1-way analysis of variance.

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