Bone Scintigram Research Articles

Hypertrophic pulmonary osteoarthropathy with primary lung cancer.

Hypertrophic pulmonary osteoarthropathy (HPO) is a rare paraneoplastic syndrome that is frequently associated with lung cancer; however, the incidence of clinically apparent HPO is not well known. The clinical data of 6,151 patients with advanced lung cancer between January 1996 and December 2008 were retrospectively analyzed in Zhejiang Cancer Hospital (Hangzhou, China). Data pertaining to the presentation of HPO, diagnosis, treatment, pathology, follow-up and clinical course were documented. HPO was confirmed using bone scintigraphy by the identification of symmetrical, abnormally high uptake in the joints, and/or long bones with digital clubbing in the extremities as well as joint pain. The clinical characteristics were investigated based on clinical and pathological records. The patients were presenting with lung cancer for the first time and had not received treatment. Among the 6,151 lung cancer patients, 115 (1.87%) demonstrated an abnormally high uptake on bone scintigraphy and digital clubbing in the extremities combined with joint pain. A total of 109 patients received surgery or chemotherapy treatment and 92 exhibited improved symptoms. The improvement rate of HPO was lower in the non-surgery compared with the surgery patients (77.4 vs. 91.1%; P=0.049). Bone scintigraphy was repeated in 85 patients within 3–6 months, and the HPO symptoms improved in 70 patients. The present retrospective study indicated that 1.87% of patients with lung cancer showed characteristics that were identified as HPO. The majority of the patient symptoms and the bone scintigram of HPO improved as a result of treatment.

Letrozole Induced Hypercalcemia in a Patient with Breast Cancer

Hypersecretion of PTHrP is a relatively common cause of malignancy-related hypercalcemia. However, there is only one case report of letrozole induced hypercalcemia. A 52-year-old female patient was referred to our clinic because of the recent discovery of hypercalcemia (11.0 mg/dL). The patient had a history of left breast carcinoma. She had started a course of letrozole (aromatase inhibitor; 2.5 mg dose/day) ten months earlier. Patient's parathyroid hormone-related protein levels were normal and a bone scintigram revealed no evidence of skeletal metastasis. Other potential causes of high calcium levels were ruled out. We recognized that, when letrozole was taken at one dose daily (2.5 mg), she had recurrent hypercalcemia. Our experience suggests that letrozole may precipitate hypercalcemia in a patient with breast cancer.

Co-existent Paget’s Disease of the Bone, Prostate Carcinoma Skeletal Metastases and Fracture on Skeletal Scintigraphy-Lessons to be Learned

Bone scintigraphy, despite being non-specific, is a very sensitive and simple investigation for patients with active Paget’s disease of the bone. Skeletal metastases and Paget’s disease may co-exist in the elderly patients as both conditions are commonly seen in this age group. Clinical and radiological correlation may help to improve the diagnostic specificity of a bone scintigram. We report a patient in whom concurrent Paget’s disease and a rib fracture became evident only on repeat scintigraphy following successful treatment of prostate carcinoma skeletal metastases.Conflict of interest:None declared.

Is retention of zoledronic acid onto bone different in multiple myeloma and breast cancer patients with bone metastasis?

Zoledronic acid (Zol) is used to treat bone disease in both multiple myeloma (MM) and breast cancer patients with bone metastasis (BC). However, bones of MM and BC patients show a difference in retention of the bisphosphonate used for bone scintigraphy. Therefore, we hypothesized that disease-specific factors may differently influence Zol retention in MM and BC patients. We tested this hypothesis in an investigator initiated phase II clinical trial in which we compared the whole-body retention (WBrt) of Zol in a cohort of 30 multiple myeloma (MM) and 30 breast cancer (BC) (20 Zol naive and 40 with six or more previous administrations). On average, 62% of the administered Zol was retained in the skeleton of both MM and BC patients and independently of the number of treatments. WBrt of Zol did not correlate with cross-linked C-telopeptide (CTX) levels, but linear regression analyses showed that WBrt of Zol correlated with bone-specific alkaline phosphatase (bALP) levels in BC (p = 0.001), and with CTX/bALP in Zol naive MM patients (p = 0.012). Especially in BC patients, WBrt correlated with age (p = 0.014) independently of kidney function. In MM patients WBrt was found to primarily correlate with the extent of bone disease (p = 0.028). Multivariate linear regression analyses of the entire cohort pointed out that WBrt of Zol was best predicted by age (p < 0.000), osseous lesions (p < 0.001), and the preceding Zol dosing (p < 0.005) (r(2) = 0.97). Comparing bone scintigrams with CT/X-ray images showed a poor correlation between sites of active bone disease and binding of scintigraphy bisphosphonate in 36% of MM patients and in 13% of BC patients. We conclude that WBrt of Zol is primarily determined by two non-disease related factors and only one disease related, but that there may be differences in retention or drug delivery at individual sites of bone disease between MM and BC patients. In order to find the optimal dosing of Zol, these observations should be taken into account.

Evaluation of Motion Correction Processing in Equine Bone Scintigraphy by Scheffé’s Method of Paired Comparisons

Equine bone scintigraphy is usually performed with horses in standing position under sedation. However, swaying motion often leads to poor-quality images. To examine the usefulness of motion correction (MC) processing, equine bone scintigrams were evaluated using Scheffé's method of paired comparisons. A significant difference in evaluation scores was detected by analysis of variance (F test, P<0.01). According to all observers, Yardstick analysis scores were higher for images use of MC processing than for those no use of MC processing, for all parts. Overall scores of 5 observers were as follows: without MC 100% acquisition time (AT, lowest), use of MC with 25% AT, MC 50% AT, MC 75% AT and MC 100% AT (highest). Thus, MC processing shortens AT in equine bone scintigraphy, and it contributes to a reduction in the external radiation exposure of nurses/technicians.

Osteomalacia secondary to renal tubular acidosis due to Sjögren's syndrome: a case report and review of the literature.

A 43-year-old woman was admitted to our hospital because of generalized bone pain. Arterial blood gas showed pH 7.266, HCO3- 13.5mEq/l, and anion gap (AG) 12. Since her urine pH was 7.0 despite metabolic acidosis with normal AG, we diagnosed distal renal tubular acidosis (RTA). Serum phosphate was 2.5mg/dl, the level of β2 microglobulin was 41100μg/l, and aminoaciduria was present. These results indicated proximal tubular dysfunction. The radiograph showed pseudofracture in the pubic bone, indicating osteomalacia. Bone scintigram showed abnormal accumulations of 99mTc-HMDP in multiple joints. Then, her generalized bone pain was considered to be a symptom of osteomalacia. Despite the absence of overt Sicca syndrome, the evaluation of Sjögren's syndrome (SjS) as a cause of distal RTA was performed. Antibodies to the SS-A level was 127U/ml. Tear break-up time was 3s bilaterally and salivary gland scintigraphy showed low uptake of 99mTc in the submandibular glands and the parotids. Thus, we diagnosed SjS finally. Gallium scintigraphy showed mild abnormal uptake in bilateral kidneys, suggesting acute tubulointerstitial nephritis. After treatment with prednisolone, alfacalcidol, and sodium bicarbonate, bone pain was remarkably relieved. Additionally, aminoaciduria disappeared and the level of β2 microglobulin decreased. We speculated that the coincidence of proximal tubular dysfunction and distal RTA cause a severe manifestation of osteomalacia.

Computer-aided diagnosis system for bone scintigrams from Japanese patients: importance of training database

AimComputer-aided diagnosis (CAD) software for bone scintigrams have recently been introduced as a clinical quality assurance tool. The purpose of this study was to compare the diagnostic accuracy of two CAD systems, one based on a European and one on a Japanese training database, in a group of bone scans from Japanese patients.MethodThe two CAD software are trained to interpret bone scans using training databases consisting of bone scans with the desired interpretation, metastatic disease or not. One software was trained using 795 bone scans from European patients and the other with 904 bone scans from Japanese patients. The two CAD softwares were evaluated using the same group of 257 Japanese patients, who underwent bone scintigraphy because of suspected metastases of malignant tumors in 2009. The final diagnostic results made by clinicians were used as gold standard.ResultsThe Japanese CAD software showed a higher specificity and accuracy compared to the European CAD software [81 vs. 57 % (p < 0.05) and 82 vs. 61 % (p < 0.05), respectively]. The sensitivity was 90 % for the Japanese CAD software and 83 % for the European CAD software (n.s).ConclusionThe CAD software trained with a Japanese database showed significantly higher performance than the corresponding CAD software trained with a European database for the analysis of bone scans from Japanese patients. These results could at least partly be caused by the physical differences between Japanese and European patients resulting in less influence of attenuation in Japanese patients and possible different judgement of count intensities of hot spots.

Duration of off-loading and recurrence rate in Charcot osteo-arthropathy treated with less restrictive regimen with removable walker

ObjectiveRecent literature on acute diabetic Charcot osteoarthropathy (CA) reports unusually long periods of off-loading. Data suggest that this might increase the re-currence rate. Subsequently we evaluated the influence of duration of off-loading on the risk of required re-casting. Research Design and MethodsIn this retrospective consecutive series from 2000 to 2005, 56 people with diabetes and an acute Charcot foot were included. The inclusion criteria were an initial persistent temperature difference more than 2°C between the two feet, oedema, and typical hot spots on a bone scintigram, radiology, and a typical clinical course. Treatment was off-loading in a removable cast and 2 crutches. In-door walking was allowed. Gradually augmented weight bearing was prescribed when the skin temperature difference had decreased to a level less than 2°C and edema had subsided. Re-casting was required for immediate exacerbation during re-load as well as for recurrence — defined as new swelling and skin temperature difference of more than 2°C in the same foot occurring after a stable interval of at least one month after full weight bearing. ResultsThe duration of off-loading for all patients was 141±21days (mean±SD). Three patients (5%) were re-casted immediately for exacerbation after re-load and 7 patients (12 %) after recurrence of the CA. Duration of re-casting was 79±44days. The primary period of off-loading was not statistically significantly different for those not requiring versus those requiring re-casting: 142±24days compared to 134±41days. Neither were the differences in demographic data, metabolic regulation, BMI or localization of CA. ConclusionsPatients with risk of exacerbation or recurrence of CA could not be identified in the present study and there was no relation to the duration of off-loading. Nevertheless off-loading periods with immobilisation should be kept as short as possible, due to other side effects. This can be obtained by early gradual augmented re-loading.

Flare hypercalcemia after letrozole in a patient with liver metastasis from breast cancer: a case report

IntroductionTamoxifen may occasionally precipitate serious and potentially life-threatening hypercalcemia. However, to date, this has not been documented with aromatase inhibitors.Case presentationA 65-year-old Japanese woman with liver metastasis from breast cancer was admitted to our hospital with vomiting, anorexia, fatigue, arthralgia, muscle pain and dehydration. She had started a course of letrozole five weeks earlier. Our patient's calcium level was 11.6 mg/dL. She was rehydrated and elcatonin was administered. Our patient's parathyroid hormone and parathyroid hormone-related protein levels were not increased and a bone scintigram revealed no evidence of skeletal metastasis. After our patient's serum calcium level returned to within the normal range, letrozole was restarted at one-half of the previous dose (1.25 mg). There were no episodes of hypercalcemia. However, 84 days after restarting letrozole, our patient again complained of arthralgia and treatment was changed to toremifene. During these periods, repeated ultrasonograms revealed no progression of liver metastasis.ConclusionTo the best of our knowledge, this is the first case report of flare hypercalcemia after treatment with letrozole in a patient with metastatic breast cancer.

Hypertrophic Osteoarthropathy as a Clinical Manifestation of Lung Cancer

Hypertrophic osteoarthropathy is a paraneoplastic syndrome most often found in non-small cell lung cancer. Diagnosis is confirmed by the presence of clubbing on physical examination and periostitis on bone scintigram, and the syndrome generally resolves with treatment of the underlying malignancy. This article presents a case study and describes symptom management options, including nonsteroidal anti-inflammatory agents, octreotide, and bisphosphonates.

Single bony lesions on 99mTc-MDP bone scintigrams of children with known malignancy

Introduction: 99mTc-MDP bone scintigraphy is employed to investigate children with known or suspected malignancy. While the presence of multiple lesions on bone scans of children in the context of known malignancy is generally considered to be due to metastases, the exact significance of solitary hot spots remains unknown. An accurate diagnosis is critical in order to determine the optimal management and eventual outcome. This study was undertaken to evaluate the significance of solitary abnormalities on bone scintigrams of children with known or suspected malignancy.

Sympathetic neuropathy in diabetes mellitus patients does not elicit Charcot osteoarthropathy

Aim The aim of the study was to determine the degree of neuropathy (autonomic and somatic) in patients with diabetes mellitus with or without Charcot osteoarthropathy (CA). Methods Forty-nine patients with diabetes mellitus type 1 or 2 were investigated. The patient population of interest was the patients with acute Charcot foot ( n=17) or chronic Charcot foot ( n=7). The inclusion criterion for an acute Charcot foot was a temperature difference of more than 2° between the two feet, oedema of the affected foot, typical hotspots in a bone scintigram and a typical clinical course. In addition, patients with first toe amputation ( n=5), a high-risk group for development of CA, and two control groups consisting of diabetes patients with ( n=9) or without somatic neuropathy ( n=11) were investigated. Regional blood flow in the feet was measured by venous occlusion plethysmography. Quantitation of somatic neuropathy was done by the Neuropathy Disability Score and modified Neuropathy Symptom Score. Quantitation of autonomic neuropathy was done by measurements of local venoarteriolar sympathetic axon reflex in the feet and of heart rate variability during deep breathing and orthostatic challenge. Results The patients with acute Charcot foot and first toe amputation had an increased blood flow in the affected foot and weakened but not absent venoarteriolar sympathetic axon reflex. In the other patient groups, a normal venoarteriolar sympathetic axon reflex in the feet was found. Conclusions Peripheral sympathetic neuropathy is not likely to be the pathophysiologic mechanism behind the hyperemia in the foot during an acute attack of CA. The hyperemia is more likely secondary to local inflammatory events.

Subchondral insufficiency fracture of the femoral head in young adults

A subchondral insufficiency fracture of the femoral head (SIF) is generally observed in elderly women. In addition, SIF has been reported to occur in young military trainees, which are considered to be due to a fatigue stress fracture. This report reviewed five cases of SIF in young adults without any history of overexertion or antecedent trauma. The clinical findings, time to the initial radiograph, time to the initial magnetic resonance imaging (MRI), and follow-up period were investigated. Radiographs and MRI were obtained in both hips. Bone mineral density and bone scintigram were performed. Measurements of a bone mineral density indicated presence of osteopenia in three patients. MRI disclosed a discontinuous irregular-shaped low-intensity band surrounded by bone marrow edema in all cases. After conservative treatments, one patient's condition resolved, while four patients underwent femoral head collapse resulting in surgical treatment. In these four patients, the diagnosis of SIF was histologically confirmed. In addition, the histological findings showed thin disconnected bone trabeculae, thus indicating the presence of some degree of osteopenia. These patients were considered to demonstrate an insufficiency fracture rather than a fatigue stress fracture based on both clinical findings and histological findings. SIF needs to be considered in patients presenting with hip pain even in young cases.

REGIONAL MIGRATORY OSTEOPOROSIS IN OLDER ADULTS: A NEW TWIST TO AN OLD DISEASE

To the Editor: A 72-year-old man presented with pain and limited motion in the right hip joint for the last 50 days. He described the symptoms as occurring mainly during walking and prolonged upright stance but not at rest. He denied any antecedent injury, and his current medical history was noncontributory. Further review of his medical files revealed that 20 years earlier he had two episodes of regional migratory osteoporosis (RMO) in the left hip (1989) (Figure 1A) and right knee (1990). He had a complete recovery under calcitonin treatment combined with a rehabilitation protocol of initial limited weight bearing followed by therapeutic exercise. (A) Anterior view from bone scintigram (1989) demonstrating avid radiotracer uptake mainly in the left hip joint. (B) Anteroposterior X-ray (2010) showing initial demineralization of right femoral head. (C) Coronal T1-weighted magnetic resonance imaging (2010) showing low signal intensity in the right femoral head and neck (bone marrow edema). His current physical examination revealed mild tenderness on palpation over the right groin area and upper thigh, atrophy of the quadriceps, pain-induced restriction in hip range of motion, and antalgic gait. Laboratory analysis, including complete blood count; erythrocyte sedimentation rate; liver, kidney, and thyroid function tests; and parathyroid hormone and vitamin D levels, was unremarkable. Hip X-ray performed 5 to 6 weeks after the onset of symptoms showed initial demineralization of the right femoral head with a thin but intact subchondral line and preserved joint space (Figure 1B). Bone mineral densitometry (lumbar quantitative computed tomography) was normal. Bone scintigraphy and magnetic resonance imaging (MRI) (Figure 1C) were consistent with transient osteoporosis of the hip (TOH),1 and overall he was diagnosed as having a recurrence of RMO, after a lapse of 20 years. He was started on a combination of alendronate, calcium, and vitamin D, with a rehabilitation protocol consisting of limited weight bearing (use of two crutches) associated with progressive non-weight-bearing strengthening exercises. After 2 months, pain and limping disappeared. RMO is an uncommon condition characterized by migrating arthralgia of the weight-bearing joints in the lower extremities associated with severe focal osteoporosis. Secondary joints are generally involved within the first year of the initial episode. Middle-aged men are most commonly affected.2 Early radiographic changes are often subtle and lag behind the clinical symptoms by 3 to 6 weeks.3 Bone scintigraphy and MRI are crucial for early diagnosis. Management is conservative and mainly directed toward pain management, osteoporosis treatment, limited weight bearing, and therapeutic exercise. TOH and RMO have been histologically considered to be a form of “high remodeling” osteoporosis,3 but their pathophysiology is under debate. It has not been established whether TOH and RMO represent distinct conditions or are part of a common spectrum of “bone marrow edema” syndromes3,4 that range from these self-limiting clinical entities to more-severe conditions, such as subchondral fractures4,5 and avascular necrosis.6 The reason this case is being reported is twofold. First, to the knowledge of the authors, this case represents the longest duration between two RMO episodes; before this, the longest interim reported in the literature was 11 years.3 Second, bearing in mind the devastating scenarios linked to some hip pathologies in older adults, physicians' attention should be drawn to the clinical problem of TOH and RMO (which can easily be overlooked), its differential diagnosis (particularly with subchondral fractures and incipient osteonecrosis of the femoral head3–6), and its possible severe complications (e.g., hip fracture), also often overlooked.7 Thus, especially in older adults with a positive history of RMO, long-term follow-up is of paramount importance. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Study concept and design: GF, LÖ, FF. Acquisition of subjects and data: GF, FF. Analysis and interpretation of data: GF, LÖ, FF. Preparation of manuscript: GF, LÖ, FF. Sponsor's Role: None.

Detection of Extensive Melorheostosis on Bone Scintigram Performed for Suspected Metastases

Melorheostosis is a rare but benign disorder characterized by asymmetric osteosclerotic dysplasia. Radiographic appearances are characteristic and described as "melting wax flowing down a candle." This disorder may involve more than one bone contiguously across the joints following a sclerotomal distribution. It is often asymptomatic but occasionally presents with pain and contractures. The authors report accidental detection of bilateral upper and lower limb melorheostosis in an elderly woman with the history of breast cancer and recent onset of low back pain, which was referred for a bone scintigram for suspected metastases. The images showed bilateral femoral and tibial melorheostosis, which was subsequently confirmed on plain radiograph and by clinical follow-up.

Solitary Phalangeal Metastasis of Renal Cell Carcinoma on Bone Scintigram

Renal cell carcinoma is known to cause lytic metastasis at various sites including axial and appendicular skeleton. However, it is unusual to find an isolated metastasis of renal cell carcinoma in the distal extremity on bone scintigraphy. A 70-year-old woman with renal cell carcinoma was referred to the Nuclear Medicine Department for a bone scintigram to exclude metastasis. The whole-body planar images were unremarkable, but the local views of the hands demonstrated a solitary metastasis in the middle phalanx of the finger. This rare experience illustrates the need for including local views of extremities in a standard whole-body study.

Significance of solitary bony lesions on [99mTc]MDP bone scintigrams of children with known malignancy

Significance of solitary bony lesions on [99mTc]MDP bone scintigrams of children with known malignancy

Hypertrophic Pulmonary Osteoarthropathy as a Paraneoplastic Manifestation of Lung Cancer

This study examined the frequency of hypertrophic pulmonary osteoarthropathy (HPO) and the clinical characteristics of lung cancer with HPO. The results of 2625 lung cancer patients who underwent bone scintigraphy were reviewed to identify patients with HPO, which was diagnosed when the bone scintigram showed a diffuse, symmetric pattern of bilateral increased uptake in the long tubular bones. Clinical characteristics were investigated based on the clinical and pathologic records. Nineteen patients (0.72%) were found to have HPO: 17 were men, 17 were heavy smokers, and 13 had clinical stage IIIB or IV disease. Ten patients complained of pain or edema in the extremities, and seven of them had stage IIIB or IV disease. In four patients with clinical stage IIIB or IV disease, HPO was not detected at the first presentation, and the diagnosis was made after disease progression. The symptoms of HPO improved in two patients who underwent surgical resection but in only three of five patients who received chemotherapy. The HPO findings on the bone scintigram improved in 2 of 3 patients who underwent surgical resection and 5 of 11 patients who received chemotherapy. Less than 1% of the lung cancer patients developed HPO as a paraneoplastic manifestation. Males, heavy smokers, and advanced disease predominated in lung cancer patients with HPO. The symptoms and bone scintigram findings of HPO improved in half of the patients on treating the lung cancer.

Ultrasonographic findings for breast carcinoma with osteoclast-like giant cells.

A 72-year-old woman visited our department with an enlarged palpable mass which was 2 cm in diameter, painless, and well-demarcated. She had noticed the mass four months earlier. The family history and her past medical history were unremarkable. On arrival, a movable tumor of 2 cm in diameter was palpated in the upper-outerquadrant of the right breast. The ipsilateral axillary lymph nodes were not palpable. The blood chemistry results, including tumor markers, were normal. Mammography revealed a mass with ill-defined borders and higher central density in the right breast (Fig. 1). The tumor was seen by breast ultrasonography (Apilio, Toshiba, Tokyo, Japan) as a low echoic mass, 28 mm 9 24 mm, with ill-defined borders, irregular margins, and internal heterogeneity (Fig. 2). Doppler US (Fig. 3) and power Doppler US (Fig. 4) showed a rich blood flow in the tumor. Contrastenhanced magnetic resonance imaging (MRI) showed the tumor to be highly enhanced with irregular margins (Fig. 5). The time-intensity curve showed an early peak and plateau pattern, suggesting malignancy. Pathological findings from a core needle biopsy revealed an infiltrating ductal carcinoma of the breast. Estrogen receptor (ER) and progesterone receptor (PgR) tests were positive, and the HER-2 score was 0. No metastases were seen in the brain, lungs, liver, bones, infraclavicular lymph nodes, or axillary lymph nodes by computed tomography (CT) and bone scintigram. With a diagnosis of right breast cancer (T2N0M0 = Stage IIA), a right modified radical mastectomy and biopsy of sentinel lymph nodes were performed. According to the intra-operative rapid pathological diagnosis, the sentinel lymph nodes were negative for metastasis. The final pathological diagnosis was an invasive ductal carcinoma (papillotubular carcinoma) with OGCs (Fig. 6). Immunohistochemical analysis demonstrated that the OGCs were CD68 and vimentin positive, but negative for cytokeratin, S-100, and a-smooth muscle actin. The clinicopathological stage, according to the UICC-pTNM classification, was Stage IIA.

Hardware Failure

A 14-year-old boy was treated for nonmetastasized femoral Ewing sarcoma with inductive and consolidation chemotherapy with surgical resection of the diaphysis and with interposition of an allograft. During follow-up, a remarkable increase in osteoblastic activity in the distal osteotomy plane was observed on Tc-99m disodium hydroxymethylene diphosphonate (HDP) scintigraphy 29 months after surgery that was highly suspicious of recurrence. Revision of radiographs showed delayed consolidation, induced by failure of hardware as the cause of increased tracer uptake. This was confirmed 6 months later by scintigraphy. It is concluded that bone scintigrams should be interpreted with available conventional x-rays to avoid false-positive results.