Osteoblastic and hyperostotic craniofacial lesion detected by 99mTc-labeled methylene diphosphonate bone scintigraphy and single-photon emission computed tomography/computed tomography: a pictorial essay.

99mTc-bisphophonates bone scan, planar and single-photon emission computed tomography/computed tomography (SPECT/CT) modalities, is a commonly used technique that provides high sensitivity and specificity for detection of osseous metastases. However, besides bone metastases, SPECT/CT provides an accurate evaluation of the localization of the lesions and supplies anatomic information that can be valuable for diagnosis of nonmalignant bone diseases, occasionally disclosed in the skull. Reporting of craniofacial lesions detected by 99mTc-MDP (99mTc-labeled methylene diphosphonate) bone scintigraphy and SPECT/CT in the literature is limited. The aim of this pictorial review is to present the findings detected by 99mTc-MDP bone scintigraphy and SPECT/CT including cases under two broad categories: osteoblastic and hyperostosis craniofacial lesions.

Bone metastasis: mechanisms, therapies, and biomarkers.

Skeletal metastases are frequent complications of many cancers, causing bone complications (fractures, bone pain, disability) that negatively affect the patient's quality of life. Here, we first discuss the burden of skeletal complications in cancer bone metastasis. We then describe the pathophysiology of bone metastasis. Bone metastasis is a multistage process: long before the development of clinically detectable metastases, circulating tumor cells settle and enter a dormant state in normal vascular and endosteal niches present in the bone marrow, which provide immediate attachment and shelter, and only become active years later as they proliferate and alter the functions of bone-resorbing (osteoclasts) and bone-forming (osteoblasts) cells, promoting skeletal destruction. The molecular mechanisms involved in mediating each of these steps are described, and we also explain how tumor cells interact with a myriad of interconnected cell populations in the bone marrow, including a rich vascular network, immune cells, adipocytes, and nerves. We discuss metabolic programs that tumor cells could engage with to specifically grow in bone. We also describe the progress and future directions of existing bone-targeted agents and report emerging therapies that have arisen from recent advances in our understanding of the pathophysiology of bone metastases. Finally, we discuss the value of bone turnover biomarkers in detection and monitoring of progression and therapeutic effects in patients with bone metastasis.

Adapting palliative radiation therapy for bone metastases during the Covid-19 pandemic: GEMO position paper.

The current health crisis caused by COVID-19 is a challenge for oncology treatment, especially when it comes to radiotherapy. Cancer patients are already known to be very fragile and COVID-19 brings about the risk of severe respiratory complications. In order to treat patients safely while protecting medical teams, the entire health care system must optimize the way it approaches prevention and treatment at a time when social distancing is key to stemming this pandemic. All indications and treatment modalities must be re-discussed. This is particularly the case for radiotherapy of bone metastases for which it is possible to reduce the number of sessions, the frequency of transport and the complexity of treatments. These changes will have to be discussed according to the organization of each radiotherapy department and the health situation, while medical teams must remain vigilant about the risks of complications of bone metastases, particularly spinal metastases. In this short piece, the members of the GEMO (the European Study Group of Bone Metastases) offer a number of recommendations to achieve the above objectives, both in general and in relation to five of the most common situations on radiation therapy for bone metastases.

Bone SPECT/CT in Postoperative Spine.

Back pain is a common problem and the diagnosis and treatment depend on the clinical presentation, yet overlap between pain syndromes is common. Imaging of patients with chronic back pain in both pre- and postoperative scenarios include radiological, radionuclide, and hybrid techniques. In general, these techniques have their own advantages and limitations. The aim of surgery is to eliminate pathologic segmental motion and accompanying symptoms, especially pain. However, surgical procedures are not without complications and localizing the cause of the pain is often challenging. Radiobisphosphonate bone SPECT/CT is reported to be useful in evaluating benign orthopedic conditions and it often provides valuable information such as accurate localization and characterization of bone abnormalities. In this review, routinely used spinal surgical techniques and procedures are discussed, as well as the acute and delayed complications related to spinal surgery, the role of conventional imaging, and the potential uses of radionuclide bone SPECT/CT to diagnose pseudoarthrosis, cage subsidence, loosening and misalignment, hardware failure, and postoperative infection.

SPECT/CT in Postoperative Painful Hip Arthroplasty.

Consecutive milestones in hip arthroplasty design and surgical technique have contributed to the successful and cost-effective intervention this procedure has become today in maintaining mobility and quality of life in patients with osteoarthritis, fracture, or other hip conditions. With the increasing prevalence of hip joint replacements, the need for improved diagnostic imaging tools to guide revision surgery has risen in parallel. Over the last few years, promising data have emerged on the potential role of bone SPECT/CT imaging in the assessment of patients with recurrent pain after arthroplasty. This review summarizes the trends in hip arthroplasty surgery (partial vs total arthroplasty; cemented vs cementless arthroplasty; resurfacing arthroplasty) and prosthesis design (bearing materials; stem designs) over the last decade. In particular, the impact on the biomechanics and interpretation of bone SPECT/CT findings is discussed, with emphasis on integrative reporting in the following frequently encountered conditions: lysis/aseptic loosening, septic loosening, heterotopic ossification, periprosthetic fracture, tendinopathies, and adverse local tissue reactions. Based on the available literature data, bone SPECT/CT is increasingly being used as second-line imaging modality when conventional investigations are nondiagnostic. Further outcome research is warranted to examine whether this technique could be used earlier in patient management.

SPECT/CT in Postoperative Foot and Ankle Pain.

Postoperative pain is a clinically relevant issue in orthopedic patients, affecting more than 40% 1 year after foot and ankle surgery. Because of the very complex anatomy with many different joints and several motion axes, clinical examination and conventional imaging are sometimes not sufficient to identify a local pain generator. Local uptake of bone-seeking radiopharmaceuticals is known to correlate accurately with sites of pain generating foci and, thus, bone scintigraphy has been an established method to evaluate these respective patients for many years. However, the specificity is rather low if only planar images are acquired. The development of SPECT and especially of hybrid SPECT and CT imaging has significantly enhanced the specificity of this technique. The combination of both functional and morphological imaging, ideally performed with a dedicated SPECT/CT system to minimize misregistration owing to motion artifacts and to enhance image quality by attenuation correction, allows an early and reliable detection of pathologic bone processes, even in patients where radiological imaging with MRI or CT is hampered by metal implants. In diabetic patients with a neuropathic Charcot osteoarthropathy, infection can be differentiated from inflammatory bone alterations (causing bone marrow edema) almost certainly using SPECT/CT with radiolabeled white blood cells and antigranulocyte antibodies, allowing an individual and precise treatment planning either in the initial course of the disease or even after surgery. This article reviews the most frequent clinical challenges in patients after foot and ankle surgery, including a description of the various surgical procedures, the different imaging options with their advantages and disadvantages, and aims to integrate bone SPECT/CT into the clinical diagnostic workup.

SPECT/CT in the Postoperative Painful Knee.

This review summarizes the role of SPECT/CT in patients with a painful postoperative knee and describes typical diagnostic criteria in these patients. Pain after knee surgery is common and is influenced by the underlying pathology, the type of surgery, and the patient. Knee joint-preserving surgery includes osteotomy, ligament reconstruction, meniscus surgery, and cartilage repair procedures, often used in combination. Knee arthroplasty procedures consist of unicondylar, patellofemoral, and primary or revision total knee prosthesis. In patients with pain after knee joint-preserving surgery, MRI remains the reference standard. After ligament reconstruction, CT can evaluate postoperative tunnel positioning, and bone SPECT/CT can contribute by assessing overloading or biodegradation problems. After meniscal or cartilage surgery, SPECT/CT can be particularly helpful to identify compartment overloading or nonhealing chondral or osteochondral lesions as cause of pain. SPECT/CT arthrography can assess cartilage damage at an early stage due to altered biomechanical forces. After corrective osteotomy of the knee, SPECT/CT can reveal complications such as overloading, nonunion, or patellofemoral problems. After arthroplasty, conventional radiographs lack both sensitivity to detect aseptic loosening and specificity in differentiating aseptic from infectious loosening. Secondly, hardware-induced artifacts still hamper CT and MRI, despite improving and increasingly available metal artifact reduction techniques. Bone scintigraphy is a proven useful adjunct to conventional radiography and MRI to reveal the pain generator and is less hampered by artifacts from metallic implants compared with CT and MRI. Nevertheless, the optimal imaging strategy in evaluating complications after knee arthroplasty is still a matter of debate. Although the evidence of the use of BS SPECT/CT is still limited, it is growing steadily. In particular, recent data on specific uptake patterns in tibial and femoral zones after total knee arthroplasty and the impact of integrating biomechanics into the assessment of SPECT/CT appear promising, but more research is needed.

Osteopenia and fractures associated with long-term therapy with MEK inhibitors.

Targeted therapies have markedly improved the survival of patients with melanoma. We report the case of two patients with advanced melanoma controlled by long-term MEK inhibitor or combination of BRAF and MEK inhibitors, who developed fractures related to severe osteopenia. A 48-year-old woman was treated by pimasertib after the failure of two lines of chemotherapy, and a 42-year-old man was treated by an association of BRAFi (dabrafenib) and MEKi (trametinib) after the failure of one line of chemotherapy. During follow-up, both complained of buttock pain, revealing primary fractures of the pelvis and lumbar vertebra. In both patients, none had osteoporosis risk factors; DEXA scan revealed osteopenia, and analysis ruled out metastatic bone lesion or secondary osteoporosis. Zoledronic acid, cholecalciferol (vitamin D3), oral calcium, and pain killers were introduced, leading to no further bone event. Numerous pathways are involved in the homeostasis of bone turnover, and the effect of tyrosine kinase inhibitors on those pathways is not well known yet. The absence of usual causes of osteoporosis or metastatic bone lesion and kinetics of symptoms lead us to suggest that MEK inhibitors were responsible for the development of osteoporosis. To the best of our knowledge, this is the first report of fractures associated with osteopenia in patients treated with MEKi. Long-term survival owing to new targeted treatment could be associated with yet underestimated adverse effects such as osteopenia/osteoporosis that could impair patient's quality of life and should be investigated.

Bone scan usefulness in patients with painful hip or knee prosthesis: 10 situations that can cause pain, other than loosening and infection.

In recent years, with the higher median life expectancy, the number of hip and knee replacements has increased. Clinical examination and morphological studies are essential to evaluate patients with a painful arthroplasty. Nuclear medicine examinations also play an important role, their main usefulness being the exclusion of prosthesis complications. Nevertheless, conventional examinations, namely bone scan and white blood cell scintigraphy, can also identify complications, such as loosening and infection. This study describes the normal and pathologic patterns of a bone scan and exemplifies ten common situations that can cause pain in patients with hip or knee arthroplasty, other than loosening and infection, which can be disclosed on a bone scintigraphy. The ten situations that should be considered and looked for when analysing a bone scan are: referred pain, patellofemoral pain syndrome, fractures, fissures, abscess/haematoma, bone insert behaviour, heterotopic ossification, greater trochanter pseudarthrosis, osteoarthritis extension in a knee with an unicompartmental prosthesis, and systemic disease with bone involvement.

Efficacy of zoledronic acid in Erdheim-Chester disease: A case report.

Erdheim-Chester disease is rare form of non-Langerhans cell histiocytosis characterized by organ infiltration of CD68+ CD1a- histiocytes. Between 500 and 600 cases have been reported. It is a multifaceted disease ranging from a solely asymptomatic bone to a fatal multisystem pattern. Bone involvement occurs in more than 90% of cases. Although not life-threatening, bone localizations can be responsible of difficult-to-treat pain and disability. Treatment depends on lesion severity. Bisphosphonates have been reported to be efficient and safe in bone involvement. We report a case of a biopsy proven bone Erdheim-Chester disease in a 65-year-old woman with history of breast cancer. Her pain was relieved after 3 perfusions of zoledronic acid and the efficiency remained at one year of follow-up.

18F-fluoride PET/CT aspect of an unusual case of Erdheim-Chester disease with histologic features of Langerhans cell histiocytosis.

We report the case of a 63-year-old woman with Erdheim-Chester disease (ECD) and histologic features of Langerhans cell histiocytosis, both extremely rare histiocytic proliferations responsible of skeletal and extraskeletal involvement. 18F-Fluoride PET/CT revealed multiple intense focal uptake scattered throughout the skeleton. We also performed an 18F-FDG PET/CT which point out visceral and vascular involvement. This case illustrates the interest of PET/CT in ECD, a rare polymorphus and systemic disease, and in our knowledge, this is the first reported illustration of 18F-fluoride PET/CT findings in this pathology.

Can we achieve a radionuclide radiation dose equal to or less than that of 99mTc-hydroxymethane diphosphonate bone scintigraphy with a low-dose 18F-sodium fluoride time-of-flight PET of diagnostic quality?

PURPOSE: 18F-Sodium fluoride is a bone tracer with a high signal-to-noise ratio, but its dosimetry is higher than that of 99mTc-labeled phosphonates at the recommended activities. The study's purpose was to determine whether the reduction by half of F-sodium fluoride-injected activity, mimicked by a short-timed reconstruction image, simulating a total dose less than or equal to that of 99mTc-hydroxymethane diphosphonate scintigraphy, had an impact on the accuracy of PET semiquantitative measurements and image quality. METHODS: Whole-body time-of-flight 18F-sodium fluoride PET/computed tomography (CT) images were acquired prospectively from 40 adult patients for detection of bone metastases. 18F-Sodium fluoride was administered according to the European Association of Nuclear Medicine (EANM) and Society of Nuclear Medicine (SNM) practice guidelines. From the acquired 1 min/bed position list-mode data, 30-s reconstructions were extracted. Measurements of maximum standard uptake value were recorded with a region of interest applied to the same location on the 1-min and 30-s images, which were displayed side by side, and were analyzed using Bland-Altman plots. A masked reading was performed by two senior nuclear medicine physicians who counted the foci of visually increased uptake. RESULTS: Bland-Altman plots showed an excellent agreement between the maximum standard uptake value measurements of the 60- and 30-s images. The paired Wilcoxon test results between the corresponding 60- and 30-s images read by masked readers A and B were not significant (P=0.15 and 0.19, respectively). CONCLUSION: Reducing acquisition duration by half or injecting half of the activity recommended by the EANM and SNM practice guidelines can lead to 18F-sodium fluoride time-of-flight PET images of diagnostic quality, achieving a radiation dose less than or equal to that of 99mTc-labeled phosphonates.