Radionuclide Bone Scan Research Articles

Effects of crystalline phase on the biological properties of collagen–hydroxyapatite composites

The objective of this study was to investigate the effects of spatial structure and crystalline phase on the biological performance of collagen–hydroxyapatite (Col–HA) composite prepared by biomineralization crystallization. Two types of Col–HA composites were prepared using mineralization crystallization (MC composites) and pre-crystallization (PC composites), respectively. Structural characteristics were analyzed by scanning electron microscopy and transmission electron microscopy. Surface elemental compositions were measured by electron spectroscopy for chemical analysis (ESCA). These composites were used in in vivo repair of bone defects. The effects of the crystalline phase on the biological performance of Col–HA composites were investigated using radionuclide bone scan, histopathology and morphological observation. It was observed that in MC composites, HA was located on the surface of the collagen fibers and aggregated into crystal balls, whereas HA in PC composites was scattered among the collagen fibers. ESCA showed that phosphorus and calcium were 8.99% and 17.56% on MC composite surface, compared with 4.39% and 5.86% on the PC composite surface. In vivo bone defect repair experiments revealed that radionuclide uptake was significantly higher in the area implanted with the PC composite than in the contralateral area implanted with the MC composite. Throughout the whole repair process, the PC composite proved to be superior to the MC composite with regard to capillary-forming capacity and the amount of newly formed bone tissue. So it could be concluded that HA placement on collagen fibers affected the biological performance of Col–HA composites. Pre-crystallization made HA scattered among collagen fibers, creating a better structure for bone defect repair in comparison with MC Col–HA composites.

CHARACTERISTIC BRAIN MRI APPEARANCE OF ERDHEIM-CHESTER DISEASE

Erdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis of unknown origin characterized by systemic infiltrates of non-Langerhans histiocytes, usually involving multiple organs, including CNS.1–3 Skeletal involvement is considered highly specific and typical radionuclide bone scan findings include bilateral, symmetric increased tracer uptake in the metaphyses and diaphyses of the long bones, mainly femur and tibiae, with epiphyseal sparing.3 Once suspected in the living patient, the diagnosis of ECD needs to be confirmed by surgical biopsy of the affected tissues. Clinical manifestations are protean4 and in cases with neurologic involvement MRI can help diagnosis.5 We report 2 cases of adult-onset ECD with neurologic involvement and strikingly similar brain MRI pattern of abnormalities. ### Case 1. A 65-year-old man was admitted with a 4-year history of progressive loss of coordination and balance. He had had central diabetes insipidus for 3 years. Neurologic examination showed cerebellar ataxia and pyramidal signs. Dysarthria and dysphagia were also present, suggesting possible supranuclear bulbar involvement. Sensory, cognitive functions, and cranial nerves were normal. Biochemical parameters, including serum sodium, potassium, magnesium, and phosphate levels, were normal. A brain MRI showed diffuse hyperintensity in the pons extending to the left middle cerebellar peduncle and lower midbrain (figure, A). Diffuse hyperintensity of the periventricular white matter and thickening of the pituitary stalk were also evident. Bone radiographs showed bilateral, symmetric …

Abstract CN02-03: Circulating tumor cells as biomarkers in the development of the androgen receptor antagonist, MDV3100

Abstract Background: Selecting targeted therapies and assessing outcome in patients (pts) with castration-resistant prostate cancer (CRPC) are significant unmet medical needs. A proportion of CRPC remains dependent on androgen receptor (AR) activation. MDV3100, a second-generation AR antagonist optimized from a screen for nonsteroidal antiandrogens that retain activity in the setting of increased AR expression blocks nuclear translocation of AR and DNA binding and has no known agonist activity when AR is overexpressed. Methods: Pts with progressive CRPC were enrolled in sequential cohorts of 3–6 pts at 30, 60, 150, 240, 360, 480 and 600 mg/day. Once the safety of a dose was established, enrollment was expanded at doses >60 mg/day to include 12 chemotherapy-naïve and 12 post-chemotherapy pts per cohort. Antitumor effects were assessed using the Prostate Cancer Working Group (PCWG) 2 criteria reporting post-therapy PSA changes from baseline, and radiologic imaging for soft-tissue disease by RECIST and osseous disease on radionuclide bone scan as improved, progressed or no change. Circulating tumor cell (CTC) enumeration was performed with the FDA cleared analytically valid CellSearch assay (Veridex, LLC, Huntingdon Valley, PA) and reported as the number of cells per 7.5 ml of blood as previously described. Samples were collected at baseline, 4 weeks, and 12 weeks post-treatment and at progression of disease. Samples from outside Center were shipped overnight and processed in the CLIA certified MSKCC Clinical Chemistry laboratory. Results: A total of 140 pts were enrolled, of which 65 (46%) were chemotherapy-naïve, and 75 pts (54%) were in post-chemotherapy setting. Maximal PSA decline from baseline of ≥ 50% was achieved in 40/65 (62%) chemotherapy-naïve and 38/75 (51%) post-chemotherapy. At 12 weeks, radiographic control (no progression) was observed in 35/47 pts (74%) with evaluable soft tissue lesions per PCWG2 guidelines and 50/81 pts (62%) with bone lesions. At 600 mg/day, 2 of 3 pts had dose limiting toxicity (rash; seizure). Dose reductions due to fatigue were noted at 480 and 360 mg/day. The maximal tolerated dose was 240mg daily based on safety data. CTC counts were obtained from 128/140 (91%) pts enrolled; 16/60 pts chemotherapy-naive and 35/68 pts post-chemotherapy had ≥ 5 CTC/7.5 mL blood at baseline. CTC conversion from baseline CTC ≥ 5 (unfavorable) to CTC <5 (favorable) with treatment was noted in 75% (12/16) in chemotherapy naïve vs. 37% (13/35) in post-chemotherapy pts. In the post-chemotherapy group, patients with unfavorable CTC at baseline had a PSA decline ≥ 50% with treatment in 85% (11/13 patients) when they converted to favorable CTC counts vs. 32% (7/22) if CTC remained unfavorable (p=0.005, Fisher Exact). The PSA decline ≥ 50% was achieved in 16 of 30 (53%) pts when CTC remained favorable throughout treatment, and 1 of 3 (33%) pts with favorable baseline CTC but unfavorable CTC at follow up. In the chemotherapy naive group, CTC conversion from unfavorable to favorable was associated with PSA decline ≥ 50% in 8/12 (67%) pts compared to 1/4 (25%) in the group with a change from favorable to unfavorable, and 1/4 (25%) in the group with unfavorable CTC at baseline and follow up; when CTC stayed in the favorable category, the PSA decline ≥ 50% was achieved in 26/40 (65%) pts. Conclusions: MDV3100 demonstrated favorable efficacy assessed by prostate-specific antigen (PSA) decline and CTC enumeration. The efficacy comparable to that at higher doses and the better adverse event profile, led to the selection of 160 mg/day as the recommended dose for future studies. A prospective investigation of pre and post-therapy CTC counts and clinical outcomes in a phase III randomized, double-blind, placebo-controlled efficacy trial of MDV3100 has been recently initiated. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):CN02-03.

Evaluation of magnetic resonance imaging and radionuclide bone scan in early spondyloarthropathy

Introduction Spondyloarthropathy (SpA) comprises a small percentage of low backache (LBA) and presents with inflammatory pain. Sacroiliitis in SpAs forms the basis of diagnosis, and may take 7–8 years to become visible in plain radiographs. In order to achieve significant modification of the course of the disease it is imperative to make an early diagnosis, identify risk factors for aggressive disease and initiate the therapy right at outset. Magnetic resonance imaging (MRI) is a promising modality to pick up inflammation and structural damage early in the course of the disease. Objective To assess the role of MRI and radionuclide bone scan in patients with early SpA of less than 2 years. Methods Patients with inflammatory LBA, defined according to the Calin criteria and satisfying the European Spondyloarthropathy Study Group (ESSG) criteria for SpA of less than 2 years duration, were included. Controls had mechanical LBA. A detailed clinical assessment and assessment of disease activity and functional impairment was done with validated measures. Radiological assessment included conventional radiograph of the pelvis, radionuclide scan and MRI of sacroiliac joints (SI joints). The sensitivity, specificity and predictive value of each modality in contributing to the diagnosis of SpA were assessed. Results Assessment of 132 SI joints in 33 patients (Age 31 ± 6.14 years, M:F 24:9) and 33 controls (Age 31.8 ± 7.21 years, M:F 27:5) was done. The mean disease duration of cases was 10.7 (± 6.97) months. Conventional radiograph failed to pick up sacroiliitis in any of the cases. Positive bone scan was present in 27 patients (21 bilateral sacroiliitis, 6 unilateral sacroiliitis). Bone scan had a sensitivity of 81.8% and a specificity of 88%. MRI abnormality was present in 29 patients (50 joints, bilateral in 21 and unilateral in 8) and in none of the controls. This accounted for a sensitivity of 87.9% and a specificity of 100%. The MRI changes included bone marrow oedema (89%), synovial enhancement (55%), subchondral oedema (41%), erosions (51%) and sclerosis (28%). Both inflammatory and structural changes in MRI showed positive correlation with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ( P = 0.034, 0.02) and erythrocyte sedimentation rate (ESR) ( P = 0.02, 0.001). Conclusions In patients with early SpA of less than 2 years duration, conventional radiographs did not pick up sacroiliitis; however, both the radionuclide scan and MRI were useful.

Single-photon emission computed tomography combined with computed tomography (SPECT/CT) in bone diseases

Radionuclide bone scanning was proven effective many years ago. Its main advantages are good sensitivity, limited radiation exposure, and noninvasiveness. However, increased radionuclide uptake by a lesion is not specific, and differentiating malignant from nonmalignant disorders may therefore be difficult. An additional structural imaging study is often needed to establish the final diagnosis. Furthermore, the limited resolution of radionuclide bone scanning images does not allow accurate localization of the lesions. Single-photon emission computed tomography (SPECT) combined with computed tomography (CT) provides both structural and functional information. SPECT/CT has been proven useful for interpreting radionuclide bone scan results in patients with bone malignancies, showing far better specificity than planar imaging or SPECT alone, most notably in the evaluation of spinal abnormalities. SPECT/CT provides an accurate evaluation of the site of the lesions and also supplies other information that can be useful in nonmalignant conditions such as injuries, infections, and degenerative disease. Nevertheless, there are only a few published studies on the usefulness of SPECT/CT in nonmalignant conditions. However, SPECT/CT is only starting to become available and may become a routine investigation for a number of rheumatic disorders.

The PET and the Pendulum

Use of PET and CT for noninvasive detection of distant metastatic disease in lung cancer has been validated by many detailed studies, including Maziak and colleagues' study in this issue. Given acc...

18F-choline PET/CT imaging of RECIST measurable lesions in hormone refractory prostate cancer

Apply measurability criteria based on the response evaluation criteria in solid tumors (RECIST) to lesions found on (18)F-choline positron emission tomography (PET)/computerized tomography (CT) in patients with hormone refractory prostate cancer. Whole-body PET followed by CT or in-line PET/CT using 3.3-4 MBq/kg of (18)F-choline was performed prospectively on 30 patients with prostate cancer, castrate testosterone levels, and rising post-treatment prostate specific antigen (PSA) levels. Lesions demonstrating increased (18)F-choline uptake were classified as measurable or non-measureable based on RECIST. Three patients were known previously to have RECIST measurable lesions, 10 patients had metastatic findings on radionuclide bone scan, and 17 patients had elevated serum PSA level as the only evidence of disease. Lesions demonstrating increased (18)F-choline uptake were found in 28 (93%) patients. Thirty-eight PET/CT lesions from 14 patients were measurable by RECIST. Lymph node maximum standardized uptake value (SUV(max)) correlated with lymph node diameter (Pearson r = 0.44, p < 0. 001). RECIST measurable lymph node SUV(max) was significantly higher than that of non-measurable nodes (8.1 vs. 3.7, p < 0.0001). Detection of skeletal, prostatic, or RECIST-compatible lesions was more likely with a PSA level greater than 4.0 ng/ml (Fisher exact p = 0.0005). Lesions detected with (18)F-choline PET/CT are frequently measurable by RECIST at baseline. Therefore, it may be feasible to include comparisons to RECIST in evaluations of (18)F-choline as a therapeutic response marker for hormone refractory prostate cancer.

Laparoscopic radical nephrectomy after shrinkage of a caval tumor thrombus with sunitinib

A 57-year-old woman presented to the emergency department at a community hospital with a 2-month history of fatigue and right-sided flank and abdominal pain. Noncontrast CT of the abdomen and pelvis revealed a 9.1 cm right renal mass. Contrast CT of the chest, abdomen and pelvis, MRI of the abdomen and pelvis with gadolinium, radionuclide bone scan, lung nodule biopsy, complete blood count, comprehensive metabolic profile, and measurement of serum lactate dehydrogenase. Stage IV, T3bN0M1 clear cell renal cell carcinoma, with an associated tumor thrombus extending into the vena cava. The patient was treated with neoadjuvant sunitinib, which resulted in a marked response in the primary tumor and metastatic lesions as well as regression of the tumor thrombus well into the renal vein. Thus, laparoscopic radical nephrectomy was feasible and was achieved without hemorrhagic or wound healing complications. One month after surgery, she had evidence of disease progression in the lung and a periaortic lymph node. She was restarted on sunitinib with resultant disease stabilization, but discontinued the drug owing to toxicity. Eight months after cessation of sunitinib, she received a dendritic cell vaccine. She remains alive without evidence of disease progression 2 years after her diagnosis.

Manifestations of Ollier's disease in a 21-year-old man: a case report

IntroductionOllier's disease is a rare nonhereditary disorder characterized by multiple enchondromas with a predilection for unilateral distribution. Malignant changes in Ollier's disease may occur in adult patients. Radionuclide bone scanning is one method used to assess lesions depicted on radiographs or magnetic resonance images that are presumed to be enchondromas. Also, a bone scan may give a clue to the multifocal nature of the disease and it has been recommended that scintigraphy is useful in the monitoring of lesions and the development of any malignant transformation.Case presentationA 21-year-old man with a history of pathologic fractures of the right tibia and multiple limb surgeries related to Ollier's disease was referred to our nuclear medicine department. Radiographic assessment showed multiple radiolucent expansile lesions, suggestive of multiple enchondromas. A whole-body bone (99mTc-MDP) scan showed multiple foci of increased activity involving the proximal and distal right femur and tibia, proximal right humerus, distal right ulna, right metacarpals, metatarsals and phalyngeal tubular bones, consistent with unilateral distribution of the lesions. The long bones of the left hemi-skeleton were unremarkable, representing unilateral involvement of the skeleton. In this case, the intensity of uptake in the lesions of the lower extremity was high, raising the possibility of malignant degeneration of the enchondromas. Hence, the patient underwent surgical excision of the suspected lesions. Pathology analysis revealed their benign nature.ConclusionAlthough the malignant transformation of enchondromas is a well known phenomenon, it should be kept in mind that other etiologies can be considered as the cause of intensely increased uptake. Retrospective assessment of our patient revealed that the etiology of increased uptake in the lower limb lesions was due to previous insufficiency fractures and the possibility of malignant transformation was ruled out based on the pathology findings.

Use of radionuclide bone scans in multicenter clinical trials: Opportunities for quality improvement

e17534 Background: Radionuclide bone scans are widely utilized to screen for osseous metastases given their high sensitivity for detection of metastatic disease. However, the variance in image quality can significantly impact the diagnostic interpretation. Methods: Prospective assessment of image quality on 478 digital and hard copy planar bone scans received as part of several multi-center clinical trials was completed using a two reviewer paradigm. To improve image quality, the following steps were taken: an Internal Image Quality Task Committee was formed, a comprehensive training program for all internal quality control reviewers was completed, and a site qualification process was initiated prior to site selection and/or subject enrollment with direct feedback to the sites. Results: Significant image quality issues potentially limiting the diagnostic interpretation of the radionuclide scans were initially identified in 21% of the submitted radionuclide bone scans. Quality issues were based on: technical factors, poor imaging technique, and subject factors which could not be corrected. A discordance rate of 4.3% among the two reviewers was also measured. After institution of the above steps, the net result was a 58% decrease in the quality control issues that were previously identified. The most significant improvements occurred on the basis of the site qualification process where sites changed from sending hard copy to digital images and there was direct feedback from the Imaging Core Lab to the sites to correct identified issues. Conclusions: Image quality of bone scans in multicenter clinical trials can be improved with direct communication coupled with a site qualification process prior to subject enrollment. We suspect these quality improvements will impact event driven endpoints that rely on the accurate assessment of bone lesions. We further suspect this level of quality control will continue to increase in importance as technology evolves to include hybrid scanning techniques such as SPECT/CT. This parallels our experience in the level of quality control and site qualification required for deployment of FDG-PET imaging in multicenter clinical trials. [Table: see text]

Vitamin D Deficiency Masquerading as Metastatic Cancer: A Case Series

Patients with vitamin D deficiency can present with nonspecific bone pain and findings on radionuclide bone scanning that may suggest metastatic malignancy. In this report, we present 4 such cases, in which clinicians initially pursued diagnoses of metastatic malignancy and did not consider vitamin D deficiency and osteomalacia in the differential diagnosis. Eventual recognition of vitamin D deficiency and provision of supplementation resulted in prompt resolution of symptoms for each patient. In appropriate cases, timely consideration of a diagnosis of vitamin D deficiency can mitigate the anxiety associated with undergoing an evaluation for cancer.

Letters to the Editor

Letters to the Editor

Survey of the initial management and imaging protocols for occult scaphoid fractures in UK hospitals

The aim of this research was to survey how occult fractures of the scaphoid bone are both imaged and managed initially. A total of 832 questionnaires were sent via e-mail to active associate members of the British Orthopaedic Association. Included was a series of questions regarding the timing of initial and subsequent orthopaedic review of this group of patients and the use of serial radiographs and second-line imaging techniques. Nearly half of the UK's acute NHS trusts were represented (45%). The response rate was 16% (130 out of 832). Only 16% of respondents were aware of a local imaging protocol for the investigation of suspected fractures of the scaphoid. Ninety-four percent of respondents performed a second radiograph at first fracture clinic review. Fifty-eight percent used magnetic resonance imaging (MRI) as a second-line investigation; with computed tomography scan and radionuclide isotope bone scan being performed by 26% and 16% respondents, respectively. The survey revealed a wide variation in the management of occult fractures of the scaphoid. MRI has been shown to be both sensitive and specific in diagnosing occult carpal bone fractures. There is a need to standardise the management of these injuries to ensure early diagnosis and limit unnecessary wrist immobilisation.

A 70-year-old male having advanced prostate cancer presenting with hypercalcemia and diffuse osteoblastic bone metastases: a case report

BackgroundBony metastases were occasionally the initial presentations of malignancy. Overlooking of bony changes on radiographs in cancer patients with non-specific clinical symptoms may lead to delayed diagnosis.Case presentationWe presented a 70-year-old male having hypercalcemia and diffuse osteoblastic bone metastases on routine plain films. Finally, prostate cancer was diagnosed with a prostate needle biopsy.ConclusionAlthough the modern radionuclide bone scanning is useful in diagnosis, osteoblastic bone changes are occasionally seen in plain films, which are frequently overlooked. To avoid delayed diagnosis, bony structures should be carefully examined in all plain-film radiographs.

Adrenocortical carcinoma with skeletal metastases in a postmenopausal woman

Adrenocortical cancer is a very rare tumor with a poor prognosis. About half of them are hormone-secreting tumors. In most cases, hormonal investigations reveal an excess secretion of steroids, mostly cortisol and androgens. A 54-year-old lady presented with history of pain in left shoulder and leg for 6 months and features of virilization. CT-guided fine-needle aspiration cytology of an abdominal mass revealed the presence of a carcinoma of the left adrenal cortex. A whole-body radionuclide bone scan revealed increased uptake in the left clavicle and left femur. The patient has received palliative radiotherapy for the skeletal lesions and 3 cycles of palliative chemotherapy at present.

Does Magnetic Resonance Imaging of the Spine Have a Role in the Staging of Prostate Cancer?

Aims Magnetic resonance imaging (MRI) is an effective method for evaluating the spine in patients with a high risk of metastatic disease. The aim of this study was to compare MRI spine with radionuclide bone scan in detecting spinal metastases for staging prostate cancer patients. Materials and methods A cohort of 99 patients with locally advanced prostate cancer at high risk of skeletal metastasis (prostate-specific antigen > 10 ng/ml, composite Gleason score ≥ 8) or equivocal findings on bone scan were included in the retrospective study, and their MRI spine and bone scans were analysed. Results Ten patients were detected to have definite spinal metastasis by bone scan, whereas 12 patients had definite skeletal metastasis by MRI spine. Compared with the ‘gold standard’, derived from clinical and radiological follow-up, the sensitivities for radionuclide bone scan and that for MRI spine for detecting skeletal metastasis were 71.4 and 85.7%, respectively ( P = 0.023), whereas the specificities were 96.5 and 97.7%, respectively ( P = 0.95). Of the 34 individual metastatic lesions in the spine, 15 were concordantly positive on both scans, whereas five lesions were positive only by bone scan and 11 positive only by MRI. The addition of MRI spine in the staging for prostate cancer resulted in a change of stage and management plan in seven (7%) patients. Conclusion MRI spine has comparable specificity and slightly better sensitivity than bone scan to detect spinal metastasis from prostate cancer.

PRIMARY EXTRAGONADAL RETROPERITONEAL PURE YOLK SAC TUMOR

We describe a rare case of an extragonadal retroperitoneal pure yolk sac (endodermal sinus) tumor in the paraaortic region. Radiologic investigation, which included abdominal ultrasound ,computed tomography (CT), and magnetic resonance imaging (MRI) showed a large soft tissue mass occupying the inter paraaortic, renal, pancreatic and splenic region. Radionuclide bone scans demonstrated no bone metastases. The serum alpha fetoprotein (α-FP) level was high; however β-HCG was normal. Pathologic examination of the surgical specimen showed extragonadal yolk sac tumor. After postoperative chemotherapy, follow-up CT revealed decreased residual tumoral tissues and α-FP level returned to normal.

Evaluation of Isolated Rib Lesions With Radionuclide-Guided Biopsy

Isolated rib lesions detected on bone scanning can pose a diagnostic challenge, particularly in patients with a known primary cancer. The purpose of our study was to assess the diagnostic value of radionuclide-guided rib biopsy with an intraoperative gamma probe. We conducted a retrospective chart review of 10 patients who underwent an intraoperative gamma probe-guided rib biopsy. Rib defects were identified by radionuclide bone scan. Patients received an intravenous dose of technetium 99m methylene diphosphonate within 6 hours before surgery. The approximate location of the rib defect was scanned with a hand-held gamma probe intraoperatively; an excisional rib biopsy was performed in the area with the highest tracer activity. Median age was 54 years (range, 40 to 83) and median body mass index was 32.5 (range, 23 to 52). Seven patients had a known primary extraosseous cancer and 3 patients had no history of cancer. Seven patients had pain at the time of initial evaluation. The median operative time was 45 minutes, median operative blood loss was 25 mL, and median length of stay was 1 day. Complications occurred in 2 patients: a pneumothorax that did not require treatment and a delayed hemothorax that required tube thoracostomy. Rib biopsy was accurate in all 10 patients; metastatic disease was found in 5 of 7 cancer patients. Pain improved or resolved in 4 patients. The evaluation of isolated rib lesions using radionuclide-guided rib biopsy with an intraoperative hand-held gamma probe is accurate and potentially therapeutic. Thoracic surgeons and oncologists should be aware of this approach.

Osteosarcoma metastatic to the kidney and iatrogenic hemorrhage

A 16-year old female presented painful masses in the lumbar region 5 years after the initial diagnosis of a localized osteosarcoma of the tibia. Abdominal X-ray revealed calcified masses. A bone scan confirmed an increased uptake in the renal areas. An ultrasound-guided fine needle biopsy confirmed the diagnosis of metastases. The procedure was complicated by subcapsular hemorrhage and gross hematuria. Renal metastases from osteosarcoma are usually asymptomatic and invisible on abdominal X-rays. The diagnosis is generally established by radionuclide bone scan or abdominal CT-scan. Our observation suggests that histological documentation of these unusual clinical presentations should be carefully weighed against the risk of the procedure.

Hip Pain in an 18-year-old Man

An 18-year-old man presented with a 6-month history of left hip pain. There was no antecedent trauma but a gradual onset of pain that became persistent over the 6-month period. The patient’s pain intensified with time and a bothersome limp on the left side was affecting his activity level. He had no other complaints or constitutional symptoms, nor did he report any chest pain or shortness of breath. His medical history was unremarkable. Family medical history was significant for B cell lymphoma in the patient’s maternal grandfather. On physical examination, the patient appeared healthy with stable vital signs and no apparent distress. No regional or distant lymphadenopathy and no soft tissue mass were present around the hip. He was tender to palpation in the left groin and greater trochanter. Range of motion of the hip revealed pain with rotation, greater with external than internal rotation. Flexion and extension did not produce pain. The neurovascular exam was normal, with 2 + dorsalis pedis and posterior tibial pulses. Motor examination was 5/5 and sensation was intact throughout all dermatomes. Laboratory examination revealed an elevated white blood cell count of 12.7 · 10/lL, an elevated sedimentation rate of 21 mm/hour, and an elevated C-reactive protein of 15.4 mg/L. Imaging studies included anteroposterior and lateral radiographs (Fig. 1), radionuclide Tc-99m methylene diphosphonate bone scan (Fig. 2), computed tomography (CT) scan (Fig. 3), and magnetic resonance imaging (MRI) (Fig. 4). Based on the history, physical examination, laboratory studies, and imaging studies, what is the differential diagnosis?