Osteophytes' position in subjects with DISH and right-sided aorta: verification of the 'aortic pulsation protective effect' theory.

OBJECTIVES: To validate in a large cohort with right-sided aorta the theory that thoracic right-sided flowing osteophytes in DISH results from a 'protective' effect of the pulsating descending left-sided thoracic aorta. METHODS: Chest CTs of patients with DISH and right-sided aorta and controls with DISH and left-sided aorta were evaluated and compared on each intervertebral space (IS) for the location of the aorta (right, left, centre) and the location of the osteophyte relative to the aorta (contralateral, ipsilateral, bilateral). RESULTS: The study and control cohorts included 31 and 35 subjects, respectively (male 22/9 and female 27/8; median age 64.8/65.3 years; P = 0.86). Osteophytes contralateral to the aorta's location were recorded in the majority of ISs in both the study and control groups (47% and 60%, respectively; P > 0.05), while ipsilateral osteophytes were recorded in 6.9% and 7.7%, respectively (P = 0.002). Bilateral osteophytes located to the right and the left of the aorta were significantly more prevalent in the study group compared with the controls (17.2% and 5.4%, respectively; P = 0.04). CONCLUSIONS: Aortic pulsation plays an important role in inhibiting the development of osteophytes and results in the majority of contralateral osteophytes on both right-sided and left-sided aortas. However, since both ipsilateral and bilateral osteophytes were not at all rare in both groups, other parameters, which are yet to be established, probably contribute to the location of osteophytes.

Reduction of the Vertebral Bone Mineral Density in Patients with Hodgkin Lymphoma Correlates with Their Age and the Treatment Regimen They Received.

Nowadays, Hodgkin lymphoma (HL) has become highly curable. The young age at diagnosis and long life expectancy emphasize the importance of preventing long-term treatment side effects, including bone mineral density (BMD) loss, in these patients. We aimed to evaluate the effects of first-line therapeutic modalities on BMD dynamics in HL patients, intending to identify individuals at risk for osteopenia. Demographics, HL risk factors, treatment, including cumulative steroid doses, and BMD of 213 newly-diagnosed HL patients (median age 29 years), treated at Rambam between 2008-2016, were analyzed. The main chemotherapy regimens applied were: ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP (EB; bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, prednisone). BMD was measured using PET/CT scans. BMD loss >15% was revealed in 48% of patients at therapy completion, with osteopenia prevalence of 4% and 14% at baseline and post-therapy, respectively. Cumulative hydrocortisone equivalent doses >3400 mg/m2 correlated with significant BMD reduction. Multivariate analysis at 6 months post-therapy identified age ≥30 years and EB-regimens as significant risk factors for BMD decrease >15%. Therapy-related BMD loss is common in HL patients. Its persistence is associated with age ≥30 years and EB treatment. Reduction of cumulative steroid doses and switch to non-gonadotoxic drugs should be considered.

Q Fever Osteoarticular Infection in Children.

Q fever osteoarticular infection in children is an underestimated disease. We report 3 cases of Q fever osteomyelitis in children and review all cases reported in the literature through March 2018. A high index of suspicion is encouraged in cases of an unusual manifestation, prolonged course, relapsing symptoms, nonresolving or slowly resolving osteomyelitis, culture-negative osteomyelitis, or bone histopathology demonstrating granulomatous changes. Urban residence or lack of direct exposure to animals does not rule out infection. Diagnosis usually requires use of newer diagnostic modalities. Optimal antimicrobial therapy has not been well established; some case-patients may improve spontaneously or during treatment with a ß-lactam. The etiology of treatment failure and relapse is not well understood, and tools for follow-up are lacking. Clinicians should be aware of these infections in children to guide optimal treatment, including choice of antimicrobial drugs, duration of therapy, and methods of monitoring response to treatment..

Fortuitous administration of denosumab in breast carcinoma with osteoclastic giant cells.

Breast carcinoma with osteoclastic giant cells (OGCs) is a rare entity characterized by an admixture of giant cells and malignant epithelial cells within an inflammatory and vascular stroma. Denosumab is a monoclonal antibody that targets the pathway for osteoclast formation and activation, indicated for the prevention of skeletal-related events in patients with bone metastases, as well as for the treatment of giant cell tumor of bone. We report a patient who presented with aggressive bone recurrence of breast cancer 12 years after her original diagnosis, showing a transformed histology that included multinucleated OGCs, and that was refractory to traditional therapy. Misdiagnosed with a tumor-to-tumor metastasis of breast cancer to a giant cell tumor of bone, she was treated with denosumab for her presumed primary bone disease and had a remarkable clinical and radiological response. To the best of our knowledge, this is the first report of breast cancer with OGCs occurring initially in a metastasis while absent in the original tumor and the first description of its successful treatment with denosumab. This case sheds light on the development of giant cells in the tumor microenvironment and suggests the potential use of denosumab in the management of cancers with giant cell elements.

Ankylosing Spondylitis and Neck Pain: MRI Evidence for Joint and Entheses Inflammation at the Craniocervial Junction.

BACKGROUND: Magnetic resonance imaging (MRI), which has recently become the leading imaging modality in the study of ankylosing spondylitis (AS), has not been evaluated in the assessment of disease-specific changes at the craniocervical junction (CCJ) in patients with AS. OBJECTIVES: To describe the spectrum of active inflammatory lesions at the CCJ using MRI in a cohort of patients with AS and neck pain. METHODS: The study included 18 patients with AS presenting with neck pain and a control group of 9 fibromyalgia patients matched for age and levels of neck pain. All patients underwent a focused rheumatologic examination, X-ray of the cervical spine, and a 3T MRI study, which included STIR, CUBE T2, FSE and FSE FAT SAT sequences before and after administration of gadolinium. RESULTS: The median age of AS patients was 43 years with a median disease duration of 7 years. Fifteen of 18 patients were under biologic treatment. Seven of 18 AS patients had evidence of cervical syndesmophytes on X-ray films. Active inflammatory lesions of atlanto-occipital joints and apical and alar ligaments were detected in MRIs in 2 out of the 18 patients with AS and in none of the patients with fibromyalgia. Both AS patients with active inflammation of CCJ detected on MRI received treatment with biological agents prior to and during the study. CONCLUSIONS: Active inflammation of both entheses and joints of the CCJ can be demonstrated by MRI in patients with AS.

Femur shaft fracture following osteoid osteoma radiofrequency ablation.

INTRODUCTION: Radiofrequency ablation is an effective modality in treating osteoid osteoma while avoiding the complications of an open procedure. Its complications are usually self-limited consisting mostly of local skin burns. This report presents a major complication, a femur shaft fracture following an osteoid osteoma radiofrequency ablation. The fracture occurred approximately one year after the ablation at the site of the osteoid osteoma. DISCUSSION: Few case reports have been published regarding subtrochanteric femur fracture after ablation of an osteoid osteoma. To our knowledge this is the first report of a femoral shaft fracture following an ablation. Another unique characteristic of the presented case is the late presentation, approximately one year following ablation. Factors which may have contributed to the fracture include lateral entry point of the drill which may have weakened the femur when taking its biological and mechanical properties into account, and the fact that the patient was a soldier who was allowed to continue his military training only six weeks after the ablation. CONCLUSION: Radiofrequency ablation is an effective and relatively safe technique in treating osteoid osteomas, however the physician should be aware of the fracture risk involved, consider mechanical and biologic factors of the bone prior to drilling, and be very conservative when recommending return to high level activity. In addition, a close follow-up should be carried on after the procedure in order to supervise bone remodeling.

Added Value of SPECT/CT in the Evaluation of Benign Bone Diseases of the Appendicular Skeleton.

Bone scintigraphy is a sensitive technique to detect altered bone mineralization but has limited specificity. The use of SPECT/CT has improved significantly the diagnostic accuracy of bone scintigraphy, in patients with cancer as well as in evaluation of benign bone disease. It provides precise localization and characterization of tracer-avid foci, shortens the diagnostic workup, and decreases patient anxiety. Through both the SPECT and the CT components, SPECT/CT has an incremental value in characterizing benign bone lesions, specifically in the appendicular skeleton, as illustrated by present case series.

Atypical Femoral Fractures: Radiological Evaluation and Bisphosphonate Exposure.

BACKGROUND: Evidence suggests that prolonged bisphosphonate (BP) treatment predisposes to atypical fractures (AF), but the etiology has yet to be determined. Addressing causality begins with case identification, which requires radiological adjudication. However, many trials based their case findings on coded diagnoses. OBJECTIVES: To investigate the feasibility of case findings by the coding system and the reproducibility of radiological evaluations in two hospitals in Israel, and to compare BP exposure of AF patients to a control group with typical (intertrochanteric of femoral neck) fractures. METHODS: Diagnostic databases from 2007 to 2010 were reviewed and admission X-rays of patients were examined in two steps by two radiologists. Fractures were classified as atypical or not atypical according to published criteria. A 2:1 control group was created. Ambulatory drug acquisition was reviewed. RESULTS: Of the 198 patients who fulfilled the search criteria, 38 were classified by initial radiological opinion as AF. Subsequent radiological opinion judged 16 as not atypical. Of the AF patients, 80% were exposed to BP. Of those, 81% continued to receive BP treatment for 2.4 years after AF. Only one AF patient was discharged with suspected AF diagnosis. In the control group, 27% were exposed to BP prior to fracture (P < 0.001). CONCLUSIONS: Thorough radiological revision is mandatory for proper classification of AF, and even when performed there is significant inconsistency in interpretation. Conclusions drawn from trials based solely on coded diagnoses lead to significant bias. BP exposure was significantly higher in the AF group. Caregiver unawareness of AF leads to improper management.

Standardized quantitative measurements of wrist cartilage in healthy humans using 3T magnetic resonance imaging.

AIM: To quantify the wrist cartilage cross-sectional area in humans from a 3D magnetic resonance imaging (MRI) dataset and to assess the corresponding reproducibility. METHODS: The study was conducted in 14 healthy volunteers (6 females and 8 males) between 30 and 58 years old and devoid of articular pain. Subjects were asked to lie down in the supine position with the right hand positioned above the pelvic region on top of a home-built rigid platform attached to the scanner bed. The wrist was wrapped with a flexible surface coil. MRI investigations were performed at 3T (Verio-Siemens) using volume interpolated breath hold examination (VIBE) and dual echo steady state (DESS) MRI sequences. Cartilage cross sectional area (CSA) was measured on a slice of interest selected from a 3D dataset of the entire carpus and metacarpal-phalangeal areas on the basis of anatomical criteria using conventional image processing radiology software. Cartilage cross-sectional areas between opposite bones in the carpal region were manually selected and quantified using a thresholding method. RESULTS: Cartilage CSA measurements performed on a selected predefined slice were 292.4 ± 39 mm(2) using the VIBE sequence and slightly lower, 270.4 ± 50.6 mm(2), with the DESS sequence. The inter (14.1%) and intra (2.4%) subject variability was similar for both MRI methods. The coefficients of variation computed for the repeated measurements were also comparable for the VIBE (2.4%) and the DESS (4.8%) sequences. The carpus length averaged over the group was 37.5 ± 2.8 mm with a 7.45% between-subjects coefficient of variation. Of note, wrist cartilage CSA measured with either the VIBE or the DESS sequences was linearly related to the carpal bone length. The variability between subjects was significantly reduced to 8.4% when the CSA was normalized with respect to the carpal bone length. CONCLUSION: The ratio between wrist cartilage CSA and carpal bone length is a highly reproducible standardized measurement which normalizes the natural diversity between individuals.

Traumatic fracture through the neurocentral synchondroses of L3 vertebra in a 5-year-old child.

Neurocentral synchondroses (NCS) are growth plates that contribute to the transverse growth of the vertebra. Fractures through these NCS are very rare and none have been reported in the lumbar spine. We present a rare case of a traumatic fracture through the neurocentral synchondroses of L3 vertebra in a 5-year-old child.

Sternal pseudotumor of childhood: don't touch the lesion.

The common approach to rapidly growing peristernal lesions in young infants is oncologic consultation, imaging, and early tissue diagnosis. We represent 3 such cases with unique sonographic findings favoring nonaggressive lesions named self-limiting sternal tumors of childhood, in which a conservative approach of sonographic follow-up was chosen. We review the typical sonographic characteristics in this rather new and rare entity, separating it from the more aggressive group of lesions in this location and age group, and suggest that the classic appearance should imply a wait-and-see approach, with sonographic follow-up studies rather than invasive intervention.

[Rapidly vanishing hip--a mystery].

Rapidly destructive hip disease is a rare condition, the cause of which is yet to be clarified, and is described in the literature by scant case reports. The disease was first described by Forestier in 1957, and since then many names have been proposed to describe the rapid vanishing of the femoral head, and occasionally the acetabulum. This condition initially represents as acute hip pain, and rapidly progresses to complete vanishing of the proximal femur, within a few months. We briefly discuss the literature regarding this phenomenon, and describe a case of a female patient who suffered from complete disappearance of the femoral head within 9 weeks.

FDG PET/CT imaging in the diagnosis of osteomyelitis in the diabetic foot.

PURPOSE: Osteomyelitis, the most serious complication of the diabetic foot, occurs in about 20 % of patients. Early diagnosis is crucial. Appropriate treatment will avoid or decrease the likelihood of amputation. The objective of this study was to assess the value of FDG PET/CT in diabetic patients with clinically suspected osteomyelitis. METHODS: Enrolled in this prospective study were 39 consecutive diabetic patients (29 men and 10 women, mean age 57 years, range 28-71 years) with 46 suspected sites of foot infection. Of these 39 patients, 38 had type 2 and 1 type 1 diabetes for 4-25 years, and 28 were receiving treatment with insulin. FDG PET/CT was interpreted for the presence, intensity (SUVmax) and localization of increased FDG foci. Final diagnosis was based on histopathology and bacteriology of surgical samples, or clinical and imaging follow-up. RESULTS: Osteomyelitis was correctly diagnosed in 18 and excluded in 21 sites. Of 20 lesions with focal bone FDG uptake, 2 were false-positive with no further evidence of osteomyelitis. Five sites of diffuse FDG uptake involving more than one bone on CT were correctly diagnosed as diabetic osteoarthropathy. FDG PET/CT had a sensitivity, specificity and accuracy of 100 %, 92 % and 95 % in a patient-based analysis and 100 %, 93 % and 96 % in a lesion-based analysis, respectively, for the diagnosis of osteomyelitis in the diabetic foot. CONCLUSION: FDG PET/CT was found to have high performance indices for evaluation of the diabetic foot. The PET component identified FDG-avid foci in sites of acute infection which were precisely localized on fused PET/CT images allowing correct differentiation between osteomyelitis and soft-tissue infection.

Calcium absorption, kinetics, bone density, and bone structure in patients with hereditary vitamin D-resistant rickets.

BACKGROUND: Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is caused by mutations in the vitamin D receptor gene. Children with HVDRR suffer from severe hypocalcemia and rickets that are treatable with extremely high-dose calcium supplements. Surprisingly, spontaneous recovery of calcium metabolism occurs after the end of puberty without the need for further calcium supplementation. OBJECTIVES: To evaluate the role of vitamin D receptor in intestinal calcium absorption and bone, we investigated intestinal fractional calcium absorption (FCA), bone calcium accretion (Vo+), bone mineral density (BMD), and bone structure parameters in HVDRR patients from infancy into adulthood. PATIENTS AND METHODS: Seventeen HVDRR patients aged 1.5-37 yr were investigated. FCA and Vo+ were determined by stable-calcium isotopes. BMD was determined by dual-energy x-ray absorptiometry and bone structure by high-resolution magnetic resonance imaging. RESULTS: FCA in patients aged 1.5-17 yr was 34.9 ± 11.2% compared with 57.3 ± 2.0% in age-matched controls (P < 0.00004), whereas in patients aged 18-26 yr, it was 82.0 ± 7.8 and 53.6 ± 1.2% in controls (P < 0.001). FCA of patients older than 29 yr was comparable to controls. Patients aged 18-26 yr had higher Vo+ than controls (P < 0.02). Patients under 18 and over 29 yr of age had Vo+ comparable to controls. Femoral-neck BMD Z-score was -2.38 ± 0.3 in patients under 18 yr and 0.28 ± 0.87 in postpubertal patients (P < 0.0001). Bone structure by high-resolution magnetic resonance imaging and bone parameters of HVDRR patients and controls were similar. CONCLUSIONS: Evidence from HVDRR patients reveals that calcium absorption is highly vitamin D dependent during infancy until the end of puberty, after which there is a period of about 10 yr in which mechanisms other than vitamin D-dependent ones are substantially involved in calcium absorption.

A loss-of-function mutation in NaPi-IIa and renal Fanconi's syndrome.

We describe two siblings from a consanguineous family with autosomal recessive Fanconi's syndrome and hypophosphatemic rickets. Genetic analysis revealed a homozygous in-frame duplication of 21 bp in SLC34A1, which encodes the renal sodium-inorganic phosphate cotransporter NaPi-IIa, as the causative mutation. Functional studies in Xenopus laevis oocytes and in opossum kidney cells indicated complete loss of function of the mutant NaPi-IIa, resulting from failure of the transporter to reach the plasma membrane. These findings show that disruption of the human NaPi-IIa profoundly impairs overall renal phosphate reabsorption and proximal-tubule function and provide evidence of the critical role of NaPi-IIa in human renal phosphate handling.

Osteogenic sarcoma in a child with familial expansile osteolysis syndrome: an accidental association?

We present the first reported case of a child with familial expansile osteolysis syndrome (FEO) who developed osteogenic sarcoma (OS) of the iliac bone. A 17-year-old adolescent presented with pain and a mass on the left pelvis. He was from a family with several members who had been diagnosed with FEO, from which he also suffered. The median life expectancy of affected members of the family was reported as 25 to 30 years, with death ensuing as a result of various respiratory and cardiac complications of severe skeletal deformations, characteristic of increased bone turnover as seen in FEO. Biopsy of the patient's mass revealed chondroblastic OS. He was treated according to the P9754 protocol for patients with newly diagnosed nonmetastatic OS. Chemotherapy consisted of HD-MTX, ifosfomide, doxorubicin, and cisplatin. Complete resection of the tumor was carried out, but the patient subsequently developed metastatic disease and died (histologic response to neoadjuvant chemotherapy-85%). The patient's alkaline phosphatase level that was highly elevated before the start of chemotherapy, dropped significantly during treatment, with repeated elevation soon after definitive surgery, while he was recuperating and not on treatment. We speculate that chemotherapy affected not only the malignant cells of OS but normal osteoblasts as well, with a decreasing level of alkaline phosphatase even in the absence of any clinical and radiographic signs of OS. We also think that increased bone turnover, characteristic of a condition such as FEO, may facilitate de novo development of OS.