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Bone morphogenetic proteins (BMPs) are cytokines belonging to the transforming growth factor-β (TGF-β) superfamily. They play multiple functions during development and tissue homeostasis, including regulation of the bone homeostasis. The BMP signaling pathway consists in a well-orchestrated manner of ligands, membrane receptors, co-receptors and intracellular mediators, that regulate the expression of genes controlling the normal functioning of the bone tissues. Interestingly, BMP signaling perturbation is associated to a variety of low and high bone mass diseases, including osteoporosis, bone fracture disorders and heterotopic ossification. Consistent with these findings, in vitro and in vivo studies have shown that BMPs have potent effects on the activity of cells regulating bone function, suggesting that manipulation of the BMP signaling pathway may be employed as a therapeutic approach to treat bone diseases. Here we review the recent advances on BMP signaling and bone homeostasis, and how this knowledge may be used towards improved diagnosis and development of novel treatment modalities. This article is part of a Special Issue entitled “Muscle Bone Interactions”. [ABSTRACT FROM AUTHOR]

The aim of this guideline is to provide minimum standards for the performance and interpretation of F-NaF PET/CT scans. Standard acquisition and interpretation of nuclear imaging modalities will help to provide consistent data acquisition and numeric values between different platforms and institutes and to promote the use of PET/CT modality as an established diagnostic modality in routine clinical practice. This will also improve the value of scientific work and its contribution to evidence-based medicine. [ABSTRACT FROM AUTHOR]

Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia characterized by hypoplastic clavicles, late closure of the fontanels, dental problems and other skeletal features. CCD is caused by mutations, deletions or duplications in runt-related transcription factor 2 ( RUNX2), which encodes for a protein essential for osteoblast differentiation and chondrocyte maturation. We describe three familial cases of CCD, misdiagnosed as rickets over three generations. No mutations were detected on standard DNA sequencing of RUNX2, but a novel deletion was identified on quantitative polymerase chain reaction (qPCR) and multiple ligation-dependent probe amplification (MLPA). The present cases indicate that CCD could be misdiagnosed as rickets, leading to inappropriate treatment, and confirm that mutations in RUNX2 are not able to be identified on standard DNA sequencing in all CCD patients, but can be identified on qPCR and MLPA. [ABSTRACT FROM AUTHOR]

Adipokines derived from adipocytes are important factors that act as circulating regulators of bone metabolism. C1q/tumor necrosis factor (TNF)-related Protein-3 (CTRP3) is a novel adipokine with multiple effects such as lowering glucose levels, inhibiting gluconeogenesis in the liver, and increasing angiogenesis and anti-inflammation. However, the effects and the mechanisms of CTRP3 on bone metabolism, which is regulated by osteoblasts and osteoclasts, have not been investigated. Here, we found that CTRP3 inhibited osteoclast differentiation induced by osteoclastogenic factors in bone marrow cell-osteoblast co-cultures, but did not affect the ratio of receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) to osteoprotegerin (OPG) induced by osteoclastogenic factors in osteoblasts. We also found that CTRP3 inhibited osteoclast differentiation from mouse bone marrow macrophages (BMMs) induced by RANKL in a dose-dependent manner without cytotoxicity. Functionally, CTRP3 inhibited the F-actin formation and bone resorbing activity of mature osteoclasts. Pretreatment with CTRP3 significantly inhibited RANKL-induced expression of c-Fos and nuclear factor of activated T-cells (NFATc1), essential transcription factors for osteoclast development. Surprisingly, the activation of AMP-activated protein kinase (AMPK) was considerably increased by pretreatment with CTRP3 for 1 h. The CTRP3-stimulated AMPK activation was also maintained during RANKL-induced osteoclastogenesis. CTRP3 did not affect RANKL-induced p38, ERK, JNK, Akt, IκB, CREB, and calcium signaling (Btk and PLCγ2). These results suggest that CTRP3 plays an important role as a negative regulator of RANKL-mediated osteoclast differentiation by acting as an inhibitor of NFATc1 activation through the AMPK signaling pathway. Furthermore, CTRP3 treatment reduced RANKL-induced osteoclast formation and bone destruction in mouse calvarial bone in vivo based on micro-CT and histologic analysis. In conclusion, these findings strongly suggest that CTRP3 deserves new evaluation as a potential treatment target in various bone diseases associated with excessive osteoclast differentiation and bone destruction. [ABSTRACT FROM AUTHOR]

Low-turnover bone disease is one of the bone abnormalities observed in patients with chronic kidney disease (CKD) and is recognized to be associated with low serum parathyroid hormone (PTH) level and skeletal resistance to PTH. Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood as renal dysfunction progresses in CKD patients. A recent in vitro study using an osteoblastic cell culture system suggests that IS has an important role in the pathogenesis of low bone turnover through induction of skeletal resistance to PTH. However, the effects of IS on the progression of low bone turnover have not been elucidated. In the present study, we produced rats with low bone turnover by performing parathyroidectomy (PTX) and fed these rats a diet containing indole, a precursor of IS, to elevate blood IS level from indole metabolism. Bone metabolism was evaluated by measuring histomorphometric parameters of secondary spongiosa of the femur. Histomorphometric analyses revealed significant decreases in both bone formation–related parameters and bone resorption–related parameters in PTX rats. In indole-treated PTX rats, further decreases in bone formation–related parameters were observed. In addition, serum alkaline phosphatase activity, a bone formation marker, and bone mineral density of the tibia tended to decrease in indole-treated PTX rats. These findings strongly suggest that IS exacerbates low bone turnover through inhibition of bone formation by mechanisms unrelated to skeletal resistance to PTH. [ABSTRACT FROM AUTHOR]

OBJECT IVE: Chronic kidney disease - mineral and bone disorder (CKD -BMD) is a worldwide challenge in hemodialysis patients (HD). Widespread use and improved methods of HD may have changed the spectrum of locomotor system disorders in this population. Locomotor system disorders have an impact on health-related quality of life (QOL). The objective of this study was to assess the effect of CKD-BMD on the locomotor system (bone, joint, muscle, tendon and bursa) and document the prevalence of locomotor system disorders in HD populations and its impact in QOL. MATER IAL and MET HODS : 550 HD patients were enrolled in this study. Each HD patient received complete locomotor system examination and specific diagnostic investigation. iPTH level classified study population into three groups. Group 1. (149 patients) iPTH level < 100 pg/ml, low- turnover renal osteopathy, Group 2. (126 patients) iPTH from 150-300 pg/mL, Group 3. (275 patients) iPTH > 300 pg/ mL, high turnover bone disease. Patients were offered a self-administered QOL questionnaire, which assessed various QOL variables. RESU LTS : 75% of hemodialysis patients suffered from one or more locomotor system disorders and the commonest was bone pain 60%, followed by muscle cramps 36%, proximal muscle weakness 30%, osteoarthritis 25%, osteoporosis 16%, rotator cuff syndrome15%, gout pre-HD 12.5%, carpal tunnel syndrome 12%, bone fracture 7%, fibromyalgia 7%, tenosynovitis 6%, periarticular calcification 5%, Dupuytren's contracture 2%, septic arthritis 0.9% and osteomyelitis 0.9%. The three studied groups were represented by 27%, 23% and 50% respectively. The prevalence of osteoarthritis, muscle cramps, bone pain, spontaneous bone fracture and osteoporosis were higher in the third group. 30% of our HD patients completed the QOL questionnaire without assistance and their mean functional status, psychological status, pain scale, fatigue scale, global assessment and joint count were 3.24±2.24, 3.13 ±1.67, 4.07 ±1.7, 4.95 ±1. 8, 3.97 ±1.55 and 9.65±9.95 respectively. QOL variables pronouncedly worsen in HD patients, however the second group patients have a better quality of life than other groups (P<0.001). CONCLUS ION: Locomotor system involvement is still very common in our HD patients, especially in high turnover bone disease group and can compromise the QOL. [ABSTRACT FROM AUTHOR]

We describe a case of development of painful periostitis deformans in a 39-year-old woman who was receiving long-term voriconazole treatment for Aspergillus infection as a complication of orthotopic liver transplant. Measurement of fluoride levels strongly supports fluorosis to be the mechanism of the voriconazole-induced periostitis deformans and supports the concept that such measurements might be of use in predicting this complication of long-term voriconazole treatment. [ABSTRACT FROM AUTHOR]

Objective To determine the diagnostic and prognostic significance of cardiac magnetic resonance imaging (CMRI) in a cohort of patients with eosinophilic granulomatosis with polyangiitis (EGPA). Methods We conducted a monocentric retrospective study including 42 EGPA patients who had consecutively undergone CMRI at diagnosis or during follow-up, independently of signs of cardiac involvement. Results Forty-two patients (male 59.5%, mean age at diagnosis 46.5 years) were included. ANCA was positive in 26.2%, and median EGPA duration before the 1st CMRI screening was 5 months. Seventeen (40.5%) were diagnosed with cardiomyopathy, independently of CMRI findings. CMRI showed myocardial late gadolinium enhancement (LGE) in 82.4% patients with cardiomyopathy vs. 44% without cardiomyopathy (P = 0.024). Using LGE as the sole criterion, CMRI sensitivity and specificity for diagnosing cardiomyopathy were 82.4% and 56%, respectively. Among the 15 patients with cardiomyopathy who underwent additional CMRI during follow-up, CMRI-detected cardiac lesions had improved in 7 patients, while those of 8 patients worsened or stabilized despite treatment. These latter patients presented with significantly more cardiac events during follow-up (P = 0.026). No differences were found between non-cardiomyopathic patients with or without CMRI anomalies concerning EGPA cardiac manifestations and outcomes. Conclusion The diagnostic significance of myocardial LGE in EGPA patients remains uncertain and should not be the only criterion for cardiomyopathy diagnosis. For patients with no other signs of cardiomyopathy, CMRI-detected anomalies do not seem to adversely affect prognosis or outcome. For patients with cardiomyopathy, CMRI reassessment seems promising in detecting patients with a less favorable cardiac outcome. [ABSTRACT FROM AUTHOR]

An interview is presented with Stephen L. Kates and Edward M. Schwarz, senior authors of the study "A Diagnostic Serum Antibody Test for Patients With Staphylococcus aureus Osteomyelitis." Topics covered include winning the 2015 CORR ORS Richard A. Brand Award for Outstanding Orthopaedic Research, diagnostic testing in orthopedics, the use of an immunologic approach to help prevent infections safely, and the diagnostic potential of antibody-secreting cells.

Background: Gorham's syndrome is a rare illness of unknown etiology. It is characterized by a local proliferation of blood or lymphatic vessels that in bones leads to progressive resorption and destruction. The cause of the disease is not elucidated, and therapeutic options remain limited. Case presentation: We report herein the case of a young female Caucasian patient aged 18 years with diffuse Gorham syndrome. In tissue specimens angiogenesis and massive lymphangiogenesis as well as the expression of vascular endothelial growth factor-A (VEGF-A) and neuropilins was observed. Lymphangiogenesis is a prominent feature of the disease and a number of lymphatic markers were found to be expressed, however only VEGF-A, but not vascular endothelial growth factor-C (VEGF-C) was found to be elevated in the circulation. Circulating levels of soluble VEGF receptor-1 were also not elevated. Furthermore, the patient responded favorably and the disease was stabilized following treatment with the beta-blocking agent Propranolol alone which acts on VEGF-A alone, but not on soluble VEGF receptor-1 levels. Conclusion: This suggests that the disease is dependent on VEGF-A, but on neither VEGF-C, the major driver of lymphangiogenesis, nor FLT1. Furthermore, Propranolol acts on VEGF-A but not FLT1 expression. [ABSTRACT FROM AUTHOR]

Obesity is generally recognized as a condition which positively influences bone mass and bone mineral density (BMD). Positive effect of high body mass index (BMI) on bone has been recognized as a result of increased mechanical loading exerted on the skeleton. However, epidemiologic studies indicate that obesity is associated with increased incidence of fractures. The results presented here offer a new perspective regarding the mechanisms which may be responsible for the increase of bone mass and concurrent decrease in bone quality. Two groups of 12 week old C57BL/6 males were fed either high fat diet (HFD) or regular diet (RD) for 11 weeks. Metabolic profile, bone parameters and gene expression were assessed in these groups at the end of the experiment. Additionally, bone status was evaluated in a third group of 12 week old animals corresponding to animals at the start of the feeding period. Administration of HFD resulted in development of a diet-induced obesity (DIO), glucose intolerance, alteration in energy metabolism, and impairment in WAT function, as compared to the age-matched control animals fed RD. The expression of adiponectin, FABP4/aP2, DIO2 and FoxC2 were decreased in WAT of DIO animals, as well as transcript levels for IGFBP2, the cytokine regulating both energy metabolism and bone mass. At the end of experiment, DIO mice had higher bone mass than both control groups on RD, however they had decreased bone formation, as assessed by calcein labeling, and increased marrow adipocyte content. This study suggests that the bone mass acquired in obesity is a result of a two-phase process. First phase would consist of either beneficial effect of fat expansion to increase bone mass by increased mechanical loading and/or increased production of bone anabolic adipokines and/or nutritional effect of fatty acids. This is followed by a second phase characterized by decreased bone formation and bone turnover resulting from development of metabolic impairment. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the usefulness of the metal artifact reduction technique 'WARP' in the assessment of metal-on-metal hip resurfacings at 1.5 and 3T in the context of image quality and imaging speed. Materials and methods: Nineteen patients (25 hip resurfacings) were randomized for 1.5 and 3T MRI, both including T1 and T2 turbo spin-echo as well as turbo inversion recovery magnitude sequences with and without view angle tilting and high bandwidth. Additional 3T sequences were acquired with a reduced number of averages and using the parallel acquisition technique for accelerating imaging speed. Artifact size (diameter, area), image quality (5-point scale) and delineation of anatomical structures were compared among the techniques, sequences and field strengths using the Wilcoxon sign-rank and paired t-test with Bonferroni correction. Results: At both field strengths, WARP showed significant superiority over standard sequences regarding image quality, artifact size and delineation of anatomical structures. At 3T, artifacts were larger compared to 1.5T without affecting diagnostic quality, and scanning time could be reduced by up to 64 % without quality degradation. Conclusion: WARP proved useful in imaging metal-on-metal hip resurfacings at 1.5T as well as 3T with better image quality surrounding the implants. At 3T imaging could be considerably accelerated without losing diagnostic quality. [ABSTRACT FROM AUTHOR]

Objective: To assess the clinical success and costs of computed tomography (CT)-guided radiofrequency ablation (RFA) of osteoblastoma (OB) and spinal osteoid osteoma (OO). Materials and methods: Nineteen patients with OB and eight patients with spinal OO were treated with CT-guided RFA. The OBs were localized in the extremities ( n = 10), the vertebral column ( n = 2), and (juxta-)articular ( n = 7). Dedicated procedural techniques included three-dimensional CT-guided access planning in all cases, overlapping RFA needle positions (median, two positions; range, 1-6 RF-electrode positions) within the OB nidus (multiple ablation technique, n = 15), and thermal protection in case of adjacent neural structure in four spinal OO. The data of eight operated OB and ten operated spinal OO patients were used for comparison. Long-term success was assessed by clinical examination and using a questionnaire sent to all operated and RFA-treated patients including visual analogue scales (VAS) regarding the effect of RFA on severity of pain and limitations of daily activities (0-10, with 0 = no pain/limitation up to 10 = maximum or most imaginable pain/limitation). Results: All patients had a clear and persistent pain reduction until the end of follow-up. The mean VAS score for all spinal OO patients and all OB patients treated either with RFA or with surgical excision significantly decreased for severity of pain at night, severity of pain during the day, and both for limitations of daily and of sports activities. Conclusions: RFA is an efficient method for treating OB and spinal OO and should be regarded as the first-line therapy after interdisciplinary individual case discussion. [ABSTRACT FROM AUTHOR]

Distal semitendinosus tears have been infrequently reported in the radiology literature, and a detailed description of the anatomy and imaging features of these injuries is lacking. The semitendinosus tendon is clinically relevant, as it is frequently grafted in knee ligament reconstructions and plays an important role in performing competitive activities. We present a case of a 31-year old man who developed a partial semitendinosus tear during competitive training. This case highlights the common clinical and imaging findings found with distal semitendinosus tears, and explores the various modalities available to treat this injury. We also review the clinically pertinent anatomy of the distal semitendinosus tendon and discuss the pitfalls that musculoskeletal radiologists may encounter, to avoid misdiagnosing these rare injuries. [ABSTRACT FROM AUTHOR]

Background: Determining the magnitude of glenoid bone loss in cases of shoulder instability is an important step in selecting the optimal reconstructive procedure. Recently, a formula has been proposed that estimates native glenoid width based on magnetic resonance imaging (MRI) measurements of height (1/3 X glenoid height + 15 mm). This technique, however, has not been validated for use with computed tomography (CT), which is often the preferred imaging modality to assess bone deficiencies. Purpose: The purpose of this project was 2-fold: (1) to determine if the MRI-based formula that predicts glenoid width from height is valid with CT and (2) to determine if a more accurate regression can be resolved for use specifically with CT data. Study Design: Descriptive laboratory study. Methods: Ninety normal shoulder CT scans with preserved osseous anatomy were drawn from an existing database and analyzed. Measurements of glenoid height and width were performed by 2 observers on reconstructed 3-dimensional models. After assessment of reliability, the data were correlated, and regression models were created for male and female shoulders. The accuracy of the MRI-based model's predictions was then compared with that of the CT-based models. Results: Intra- and interrater reliabilities were good to excellent for height and width, with intraclass correlation coefficients of 0.765 to 0.992. The height and width values had a strong correlation of 0.900 (P < .001). Regression analyses for male and female shoulders produced CT-specific formulas: for men, glenoid width = 2/3 X glenoid height + 5 mm; for women, glenoid width = 2/3 X glenoid height + 3 mm. Comparison of predictions from the MRI- and CT-specific formulas demonstrated good agreement (intraclass correlation coefficient = 0.818). The CT-specific formulas produced a root mean squared error of 1.2 mm, whereas application of the MRI-specific formula to CT images resulted in a root mean squared error of 1.5 mm. Conclusion: Use of the MRI-based formula on CT scans to predict glenoid width produced estimates that were nearly as accurate as the CT-specific formulas. The CT-specific formulas, however, are more accurate at predicting native glenoid width when applied to CT data. Clinical Relevance: Imaging-specific (CT and MRI) formulas have been developed to estimate glenoid bone loss in patients with instability. The CT-specific formula can accurately predict native glenoid width, having an error of only 2.2% of average glenoid width. [ABSTRACT FROM AUTHOR]

Background: Glenoid bone loss is a common finding in association with anterior shoulder instability. This loss has been identified as a predictor of failure after operative stabilization procedures. Historically, 20% to 25% has been accepted as the "critical" cutoff where glenoid bone loss should be addressed in a primary procedure. Few data are available, however, on lesser, "subcritical" amounts of bone loss (below the 20%-25% range) on functional outcomes and failure rates after primary arthroscopic stabilization for shoulder instability. Purpose: To evaluate the effect of glenoid bone loss, especially in subcritical bone loss (below the 20%-25% range), on outcomes assessments and redislocation rates after an isolated arthroscopic Bankart repair for anterior shoulder instability. Study Design: Cohort study; Level of evidence, 3. Methods: Subjects were 72 consecutive anterior instability patients (73 shoulders) who underwent isolated anterior arthroscopic labral repair at a single military institution by 1 of 3 sports medicine fellowship-trained orthopaedic surgeons. Data were collected on demographics, the Western Ontario Shoulder Instability (WOSI) score, Single Assessment Numeric Evaluation (SANE) score, and failure rates. Failure was defined as recurrent dislocation. Glenoid bone loss was calculated via a standardized technique on preoperative imaging. The average bone loss across the group was calculated, and patients were divided into quartiles based on the percentage of glenoid bone loss. Outcomes were analyzed for the entire cohort, between the quartiles, and within each quartile. Outcomes were then further stratified between those sustaining a recurrence versus those who remained stable. Results: The mean age at surgery was 26.3 years (range, 20-42 years), and the mean follow-up was 48.3 months (range, 23-58 months). The cohort was divided into quartiles based on bone loss. Quartile 1 (n = 18) had a mean bone loss of 2.8% (range, 0%-7.1%), quartile 2 (n = 19) had 10.4% (range, 7.3%-13.5%), quartile 3 (n = 18) had 16.1% (range, 13.5%-19.8%), and quartile 4 (n = 18) had 24.5% (range, 20.0%-35.5%). The overall mean WOSI score was 756.8 (range, 0-2097). The mean WOSI score correlated with SANE scores and worsened as bone loss increased in each quartile. There were significant differences (P < .05) between quartile 1 (mean WOSI/SANE, 383.3/62.1) and quartile 2 (mean, 594.0/65.2), between quartile 2 and quartile 3 (mean, 839.5/52.0), and between quartile 3 and quartile 4 (mean, 1187.6/46.1). Additionally, between quartiles 2 and 3 (bone loss, 13.5%), the WOSI score increased to rates consistent with a poor clinical outcome. There was an overall failure rate of 12.3%. The percentage of glenoid bone loss was significantly higher among those repairs that failed versus those that remained stable (24.7% vs 12.8%, P < .01). There was no significant difference in failure rate between quartiles 1, 2, and 3, but there was a significant increase in failure (P < .05) between quartiles 1, 2, and 3 (7.3%) when compared with quartile 4 (27.8%). Notably, even when only those patients who did not sustain a recurrent dislocation were compared, bone loss was predictive of outcome as assessed by the WOSI score, with each quartile's increasing bone loss predictive of a worse functional outcome. Conclusion: While critical bone loss has yet to be defined for arthroscopic Bankart reconstruction, our data indicate that "critical" bone loss should be lower than the 20% to 25% threshold often cited. In our population with a high level of mandatory activity, bone loss above 13.5% led to a clinically significant decrease in WOSI scores consistent with an unacceptable outcome, even in patients who did not sustain a recurrence of their instability. [ABSTRACT FROM AUTHOR]

Availability of potent antiretroviral therapy (ART) has resulted in markedly improved survival for people with human immunodeficiency virus (HIV) infection, as well as an aging HIV population. Increasing morbidity from age-related conditions has resulted in the need to understand the complex roles HIV and its treatment play in the pathogenesis of these conditions. Bone disease and fragility fractures are conditions that occur more frequently in HIV. It is therefore recommended that risk assessment for fragility fracture using the Fracture Risk Assessment Tool (FRAX) algorithm, and low bone mass by dual energy X-ray absorptiometry (DXA) scan, be performed in all patients with HIV infection over the age of 50 years and in those with a history of fragility fracture, and should be repeated every 2-3 years. Because many HIV experts believe that HIV infection and its treatment is a secondary cause of osteoporosis, it should be included as such in the FRAX assessment tool. Management of osteoporosis in HIV infection should follow the same guidelines as that in the general population. Attention to lifestyle factors, including vitamin D replacement, should be emphasized. Whether cessation of tenofovir- or protease inhibitor-based ART regimens should be considered prior to bisphosphonate treatment is currently unknown and should only occur in patients with active alternative ART regimens. The use of bisphosphonates has been shown to be safe and effective in HIV patients, and while there is limited data on second-line osteoporosis regimens, there is no reason to suggest they would not be effective in people with HIV. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tc-99m methylene diphosphonate [MDP] bone scan is the basis of the skeletal imaging in nuclear medicine being a highly sensitive tool for detecting bone diseases. Mechanical stimulation induced by low grade exercise or whole-body vibration appears to be advantageous regarding the maintenance and/or improvement of skeletal mass in humans. We aimed to assess the physiological influence of low grade exercise on the quality of skeletal scintigraphy using Tc-99m MDP. MATERIAL AND METHODS: Tc-99m MDP bone scan was done for 92 volunteers [Group 1; G1]. Five days later, the same subjects were re-scanned [Group 2; G2] after an exercise on treadmill for 5 minutes. Image quality was assessed using quantitative measures whereby equal regions of interest (ROI) were drawn over the femoral diaphysis, and the contralateral adductor area. The total number of counts from the bone [B] ROI and soft tissue [ST] ROI was expressed as a ratio [B:ST ratio] and a mean value for each was established. RESULTS: Statistically significant difference was found between the B:ST ratio means [p = 0.001] in G1 and G2. CONCLUSION: This study raised a physiological influence of low grade exercise on the image quality of tc-99m MDP skeletal scintigraphy by increasing MDP osseous uptake. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy initiation for HIV-1 infection is associated with 2% to 6% loss of bone mineral density (BMD). Objective: To evaluate the effect of vitamin D3 plus calcium supplementation on bone loss associated with antiretroviral therapy initiation. Design: 48-week prospective, randomized, double-blind, placebo-controlled study. (ClinicalTrials.gov: NCT01403051) Setting: 39 AIDS Clinical Trials Group units. Patients: Adults with antiretroviral therapy-naive HIV. Measurements: BMD by dual-energy x-ray absorptiometry, 25- hydroxyvitamin D levels, and other laboratory assessments. Results: 165 eligible patients were randomly assigned (79 received vitamin D3 plus calcium and 86 received placebo). The study groups were well-balanced at baseline: 90% were men, 33% were non-Hispanic black, and the median CD4 count was 0.341 x 109 cells/L. At 48 weeks, the percentage of decline in total hip BMD was smaller in the vitamin D3 plus calcium group than in the placebo group: Medians were —1.36% (interquartile range [IQR], -3.43% to 0.50%) and -3.22% (IQR, -5.56% to -0.88%), respectively (P = 0.004). Similar results were seen at the lumbar spine. At 48 weeks, 90% of patients achieved HIV-1 RNA levels less than 50 copies/mL. Levels of 25-hydroxyvitamin D3 increased with vitamin D3 plus calcium but not with placebo: Median change was 61.2 nmol/L (IQR, 36.4 to 94.3) versus 1.7 nmol/L (IQR, -13.2 to 10.7) (P< 0.001). Overall, 103 patients (62%) reported 1 or more adverse event, with similar distribution between groups; no cases of hypercalcemia and 1 case of nephrolithiasis were reported in the placebo group. Limitation: No international sites were included, and follow-up was only 48 weeks. Conclusion: Vitamin D3 plus calcium supplementation mitigates the BMD loss seen with initiation of efavirenz/emtricitabine/tenofovir disoproxil fumarate. [ABSTRACT FROM AUTHOR]

Ultrasound (US) backscatter from bones depends on the mechanical properties and the microstructure of the interrogated bone. On the other hand, photoacoustics (PA) is sensitive to optical properties of tissue and can detect composition variation. Therefore, PA can provide complementary information about bone health and integrity. In this work, a comparative study of US backscattering and PA back-propagating signals from animal trabecular bones was performed. Both methods were applied using a linear frequency modulation chirp and matched filtering. A 2.2 MHz ultrasonic transducer was employed to detect both signals. The use of the frequency domain facilitates spectral analysis. The variation of signals shows that in addition to sensitivity to mineral changes, PA exhibits sensitivity to changes in the organic part of the bone. It is, therefore, concluded that the combination of both modalities can provide complementary detailed information on bone health than either method separately. In addition, comparison of PA and US depthwise images shows the higher penetration of US. Surface scan images exhibit very weak correlation between US and PA which could be caused by the different signal generation origins in mechanical versus optical properties, respectively. [ABSTRACT FROM AUTHOR]

Thirty-four human immunodeficiency virus (HIV) specialists from 16 countries contributed to this project, whose primary aim was to provide guidance on the screening, diagnosis, and monitoring of bone disease in HIV-infected patients. Four clinically important questions in bone disease management were identified, and recommendations, based on literature review and expert opinion, were agreed upon. Risk of fragility fracture should be assessed primarily using the Fracture Risk Assessment Tool (FRAX), without dual-energy X-ray absorptiometry (DXA), in all HIV-infected men aged 40-49 years and HIV-infected premenopausal women aged ⩾40 years. DXA should be performed in men aged ⩾50 years, postmenopausal women, patients with a history of fragility fracture, patients receiving chronic glucocorticoid treatment, and patients at high risk of falls. In resource-limited settings, FRAX without bone mineral density can be substituted for DXA. Guidelines for antiretroviral therapy should be followed; adjustment should avoid tenofovir disoproxil fumarate or boosted protease inhibitors in at-risk patients. Dietary and lifestyle management strategies for high-risk patients should be employed and antiosteoporosis treatment initiated. [ABSTRACT FROM AUTHOR]

A number of studies have reported the therapeutic potential of low-intensity pulsed ultrasound (LIPUS) for induction of bone repair. This study investigated whether bone regeneration might be enhanced by application of focused LIPUS to selectively stimulate fractured calvarial bone. To accomplish this, bone defects were surgically created in the middle of the skull of rats that were subsequently exposed to focused LIPUS. Bone regeneration was assessed by repeated computed tomography imaging after the operation, as well as histologic analysis with calcein, hematoxylin and eosin and proliferating cell nuclear antigen assay. At 6 wk after surgery, bone formation in the focused LIPUS-treated group improved significantly relative to the control. Interestingly, new bone tissue sprouted from focused LIPUS target points. Histologic analysis after exposure to focused LIPUS revealed that proliferating cells were significantly increased relative to the control. Taken together, these results suggest that focused LIPUS can improve re-ossification through enhancement of cell proliferation in calvarial defect sites. [ABSTRACT FROM AUTHOR]

Schimke immuno-osseous dysplasia ( SIOD) is a rare hereditary disease characterized by skeletal dysplasia, immune deficiency and progressive renal disease. Kidney involvement mainly determines the prognosis. The most common renal pathology is focal segmental glomerulosclerosis ( FSGS). Medullary nephrocalcinosis refers to the diffuse deposition of calcium salts in renal medulla and has not previously been identified in SIOD. Here we report the first case of a pediatric patient having typical features of SIOD with medullary nephrocalcinosis. [ABSTRACT FROM AUTHOR]

Background: Since the reference value is the core factor of the T-score calculation, it has a significant impact on the prevalence of osteoporosis. The purpose of this study was to determine the effects of using the Korean reference value on the prevalence of osteoporosis and on the prediction of fracture risk. Methods: We used femoral neck bone mineral density (BMD) data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2011. The Korean reference was identified by the mean and standard deviation of men and women aged 20-29 years. We compared the prevalence and the fracture risk assessment tool (FRAX™) probability obtained from the Korean reference and the NHANES III reference. Results: In men, the prevalence of osteoporosis increased when using the Korean men's reference, and the difference increased up to 9% for those in their 80s. In women, the prevalence increased when using the NHANES III reference, and the difference increased up to 17% for those in their 80s. The reference value also affected the fracture risk probability, and the difference from changing the reference value increased in women and in subjects with more clinical fracture risk factors. In major osteoporotic fractures, the difference of the risk probability was up to 6% in women aged 70-79 years with two clinical risk factors. For femoral neck fractures, the difference was up to 7% in women aged 50-59 years with two clinical risk factors. Conclusions: We confirmed that the reference value had significant effects on the prevalence of osteoporosis and on the fracture risk probability. The KNHANES 2008-2011 BMD data reflected the characteristics of the Korean BMD status well with regard to data size and study design; therefore, these data can be used as reference values. [ABSTRACT FROM AUTHOR]

Objective. The aim of the study was to assess differences in circulating osteocalcin (OC) and osteoprotegerin (OPG), as well as in their expression in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue obtained from patients with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT). Materials and method. Serum levels of OC, OPG and soluble nuclear factor-kB ligand (sRANKL) were measured in 49 women with GDM and 30 subjects with NGT between weeks 24-32 of gestation, and three months after childbirth. OC and OPG mRNA expression was measured in 23 patients with GDM and 23 women with NGT at term, using quantitative real-time RT-PCR. Results. The patients with GDM had decreased OC mRNA expression in SAT (p=0.015), lower adiponectin mRNA expression in VAT (p=0.039), and a lower circulating adiponectin level (p=0.04). Multiple regression analysis revealed that serum adiponectin was significantly associated with OC mRNA expression in SAT (b=0.49, p=0.03). Three months postpartum, the OPG/sRANKL ratio was markedly higher in the subjects with prior GDM (p=0.03) and correlated positively with HbA1c (R=0.33; p=0.04), fasting insulin (R=0.35; p=0.03) and HOMA-IR (R=0.34; p=0.04). Conclusions. In the patients with GDM decreased OC mRNA expression in SAT might be associated with a reduced stimulatory effect on adiponectin expression in adipose tissue. On the other hand, higher OPG/sRANKL ratio suggests a better protection against bone loss in the subjects with prior GDM. [ABSTRACT FROM AUTHOR]

Thalassemia intermedia (TI), also known as nontransfusion dependent thalassemia (NTDT), is a type of thalassemia where affected patients do not require lifelong regular transfusions for survival but may require occasional or even frequent transfusions in certain clinical settings and for defined periods of time. NTDT encompasses three distinct clinical forms: β-thalassemia intermedia (β-TI), Hb E/β-thalassemia, and α-thalassemia intermedia (Hb H disease). Over the past decade, our understanding of the molecular features, pathophysiology, and complications of NTDT particularly β-TI has increased tremendously but data on optimal treatment of disease and its various complications are still lacking. In this paper, we shall review a group of commonly encountered complications in β-TI, mainly endocrine and bone complications. [ABSTRACT FROM AUTHOR]

Objective: To determine the clinical utility of bone scintigraphy in patients with limb pain of suspected musculoskeletal origin. Material and Methods: All patients aged ≥18 years who were referred for diagnosis and management of limb pain were diagnosed on the basis of history, physical examination, and investigations excluding bone scintigraphy. After the presumptive diagnosis was made (the pre-test diagnosis), all subjects underwent bone scintigraphy, or if they had a previous bone scintigram for their pain condition, the results of that scintigram were reviewed. Then, the pre-test diagnosis was reviewed in light of the bone scintigraphy findings and repeat clinical assessment as needed. The post-test diagnosis was considered either as unchanged diagnosis or changed diagnosis for the region or regions of interest. Results: There were 118 females (54.8%) and 97 males (45.2%). The mean age of the entire group was 36±8.1 years (range: 18-87 years). The mean duration of the symptoms was 17.4±11.2 months (range: 1-264 months). Of the 215 subjects, 212 had a bone scintigram. Of these 212 subjects, none had a changed diagnosis. Conclusion: In the evaluation of limb pain of suspected musculoskeletal origin, scintigraphy is unlikely to alter the pre-test diagnosis or affect treatment decisions after history, physical examination, and non-scintigraphic investigations. The clinical utility of scinitigraphy in this setting is low. [ABSTRACT FROM AUTHOR]

Objective SH3 domain-binding protein 2 (SH3BP2) is a signaling adapter protein that regulates the immune and skeletal systems. The present study was undertaken to investigate the role of SH3BP2 in arthritis using 2 experimental mouse models, i.e., human tumor necrosis factor α-transgenic (hTNF-Tg) mice and mice with collagen-induced arthritis (CIA). Methods First, Sh3bp2−/− and wild-type (Sh3bp2+/+) mice were crossed with hTNF-Tg mice. Inflammation and bone loss were examined by clinical inspection and histologic and micro−computed tomography analysis, and osteoclastogenesis was evaluated using primary bone marrow-derived macrophage colony-stimulating factor-dependent macrophages (BMMs). Second, CIA was induced in Sh3bp2−/− and Sh3bp2+/+ mice, and the incidence and severity of arthritis were evaluated. Anti-mouse type II collagen (CII) antibody levels were measured by enzyme-linked immunosorbent assay, and lymph node cell responses to CII were determined. Results SH3BP2 deficiency did not alter the severity of joint swelling but did suppress bone erosion in the hTNF-Tg mouse model. Bone loss at the talus and tibia was prevented in Sh3bp2−/−/hTNF-Tg mice compared to Sh3bp2+/+/hTNF-Tg mice. RANKL- and TNFα-induced osteoclastogenesis was suppressed in Sh3bp2−/− mouse BMM cultures. NF-ATc1 nuclear localization in response to TNFα was decreased in Sh3bp2−/− mouse BMMs compared to Sh3bp2+/+ mouse BMMs. In the CIA model, SH3BP2 deficiency suppressed the incidence of arthritis and this was associated with decreased anti-CII antibody production, while antigen-specific T cell responses in lymph nodes were not significantly different between Sh3bp2+/+ and Sh3bp2−/− mice. Conclusion SH3BP2 deficiency prevents loss of bone via impaired osteoclastogenesis in the hTNF-Tg mouse model and suppresses the induction of arthritis via decreased autoantibody production in the CIA model. Therefore, SH3BP2 could potentially be a therapeutic target in rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) is a benign disorder related to the histiocytes which can infiltrate bone tissue. The most effective method for demonstrating severity of this disease is PET/CT and bone scintigraphy might show bone lesions. We present a seventeen year old male patient with disseminated LCH presented with exophtalmos and having multiple vertebral lesions which were identified by F-18 FDG PET/CT scan and diagnostic CT but not in the bone scintigraphy. [ABSTRACT FROM AUTHOR]

Objective: The purpose of the present study was to evaluate the role of diagnostic tools and management options for patients with pyogenic sacroiliitis, including potential complications. Materials and methods: This retrospective study included 16 patients with pyogenic sacroiliitis who were admitted to a single orthopaedic centre between 2007 and 2012. The following data were collected: demographics, history, radiography, magnetic resonance images (MRI), biological data, type of pathogenic agent, abscess formation, type of management, and clinical outcome. Results: Our study demonstrated that only one-fifth of the patients with lumbogluteal or hip pain had established diagnoses of suspected pyogenic sacroiliitis upon admission. MRIs confirmed this diagnosis in all cases. MRI examinations revealed joint fluid in the sacroiliac joint and significant oedema of the adjacent bone and soft tissues. In 12 of the 16 cases, erosions of the subchondral bone were encountered. Contrast-enhanced MRI revealed that 9 patients had abscesses. All patients received antibiotic therapy. Antibiotic treatment was only successful in 9 cases. The other 7 patients underwent computed tomography (CT)-guided abscess drainage. Drainage was sufficient for 4 patients, but 3 patients required open surgery. One patient required sacroiliac arthrodesis. The clinical outcomes included minimal disability ( n = 10), moderate disability ( n = 5), and full disability ( n = 1) of the spine. Conclusions: Contrast-enhanced MRI is mandatory for a reliable diagnosis. Abscess formation was observed in approximately half of the MRI-diagnosed sacroiliitis cases and required minimally invasive drainage under CT guidance or frequently open surgery. [ABSTRACT FROM AUTHOR]

It is of clinical importance to identify bone disease related to cystic fibrosis (CF) early in its course to allow therapeutic interventions that optimize bone health. To test the technical (precision) and clinical (percentage of abnormal results, correlation with clinical parameters) performance of a commercial quantitative ultrasound apparatus for radial measurements, speed of sound (SOS) was measured at the distal third of the left radius with the Omnisense 7000p apparatus (Sunlight Medical, Tel-Aviv, Israel) in a group of young adult CF patients with regular follow-up at the Brussels and Ghent University Hospital. Sixty-three (37 males) CF patients at a median (range) age of 23.5 y (18.1–39.9) were included. SOS, SOS z -score and SOS t -score were respectively 4017 ± 97 m/s, −0.31 ± 0.74 and −0.60 ± 0.78 in males and 4086 ± 97 m/s, −0.19 ± 0.75 and −0.51 ± 0.95 in females. Mean SOS t -score was significantly lower compared with the manufacturer's reference data for males ( p < 0.0001) and females ( p = 0.01). SOS z - and t -scores correlated with weight z -score and body mass index z -score in females. No significant correlation was found between SOS and forced expiratory volume in 1 s (%). Neither diabetes mellitus nor liver disease was found to influence SOS. Radial quantitative ultrasound has a precision of 0.55%. The SOS is in the low normal range in 14% of CF patients and is influenced by weight in female patients, but not by the severity of the lung disease. [ABSTRACT FROM AUTHOR]

Background Recently, analysis of bone from knockout mice identified muscarinic acetylcholine receptor subtype M3 (mAChR M3) and nicotinic acetylcholine receptor (nAChR) subunit α2 as positive regulator of bone mass accrual whereas of male mice deficient for α7-nAChR (α7KO) did not reveal impact in regulation of bone remodeling. Since female sex hormones are involved in fair coordination of osteoblast bone formation and osteoclast bone degradation we assigned the current study to analyze bone strength, composition and microarchitecture of female α7KO compared to their corresponding wild-type mice (α7WT). Methods Vertebrae and long bones of female 16-week-old α7KO (n = 10) and α7WT (n = 8) were extracted and analyzed by means of histological, radiological, biomechanical, cell- and molecular methods as well as time of flight secondary ion mass spectrometry (ToF-SIMS) and transmission electron microscopy (TEM). Results Bone of female α7KO revealed a significant increase in bending stiffness (p < 0.05) and cortical thickness (p < 0.05) compared to α7WT, whereas gene expression of osteoclast marker cathepsin K was declined. ToF-SIMS analysis detected a decrease in trabecular calcium content and an increase in C4H6N+ (p < 0.05) and C4H8N+ (p < 0.001) collagen fragments whereas a loss of osteoid was found by means of TEM. Conclusions Our results on female α7KO bone identified differences in bone strength and composition. In addition, we could demonstrate that α7-nAChRs are involved in regulation of bone remodelling. In contrast to mAChR M3 and nAChR subunit α2 the α7-nAChR favours reduction of bone strength thereby showing similar effects as α7β2-nAChR in male mice. nAChR are able to form heteropentameric receptors containing α- and β-subunits as well as the subunits α7 can be arranged as homopentameric cation channel. The different effects of homopentameric and heteropentameric α7-nAChR on bone need to be analysed in future studies as well as gender effects of cholinergic receptors on bone homeostasis. [ABSTRACT FROM AUTHOR]

Background To compare the clinical and radiological features of intra-/juxta-articular osteoid osteoma and extra-articular osteoid osteoma in skeletally immature patients, paying special attention to the skeletal complications. Methods Osteoid osteoma in 34 children (22 boys and 12 girls, mean age 10.4 years) was dichotomized according to the location of the nidus as intra-/juxta-articular (11 children) or extra-articular (23 children). The following features were compared: diagnostic delay, typical symptoms, synovitis and limited range of joint motion, response to treatment, typical radiographic findings, and skeletal complications. Results Eight of the 11 children with intra-/juxta-articular osteoid osteoma presented with synovitis in the involved joint, which led to a delayed diagnosis for a median 9.5 months. Pain disappeared in all children with surgical or medical interventions, but at the mean 4.9-year follow-up evaluation, skeletal abnormalities around the joint were noted in 5 children (4 proximal femur and 1 distal humerus) with intra-/juxta-articular osteoid osteoma, 2 of whom required subsequent surgeries for limited hip motion caused by femoroacetabular impingement and limited range of elbow motion, respectively. In contrast, typical clinical and radiological features were observed more often in extra-articular osteoid osteoma, and only 1 child showed overgrowth of the tibia, which did not have clinical significance. Conclusions Intra-/juxta-articular osteoid osteomas in growing children exhibit different clinical and radiological features from extra-articular lesions. Skeletal abnormalities mainly develop in intra-/juxta-articular osteoid osteoma, and these may lead to permanent skeletal sequelae. [ABSTRACT FROM AUTHOR]

The article presents the case of a woman with an osteochondroma in her left hip with adjacent bursal chondromatosis, a condition that involves osteochondral bodies in a fluid-filled bursa. Topics include whether the condition arose due to benign neoplasia of cells in the bursa, whether it was caused by loose cartilage in the osteochondromatous cap, and whether surgery successfully reversed the condition.

Background: Idiopathic osteosclerosis is a localized growth of compact bone with an unknown cause. This asymptomatic lesion is an insignificant finding and as such requires no treatment. It should be distinguished from other types of osteosclerosis created by inflammatory processes and systemic diseases. Purpose: To determine the prevalence and distribution of idiopathic osteosclerosis in the jawbones in Iran and to compare this prevalence and distribution with other populations. Material and Methods: This cross-sectional descriptive study was performed in the Dental School of Shahid Beheshti University of Medical Sciences, Tehran, between 2010 and 2011. Data were collected from the files of patients who underwent panoramic radiography for dental treatment. Location, shape, and relation between idiopathic osteosclerosis and the tooth as well as the resorption of the tooth involved were evaluated. Lesion distribution regarding age, gender, localization, shape, dental relationship, and root resorption was assessed using the chi-squared test. Results: In total, 787 panoramic radiographs of 456 women and 331 men were assessed. Idiopathic osteosclerosis was detected in 75 (9.5%) patients. The prevalence of idiopathic osteosclerosis was significantly higher in the women (11.8% vs. 6.3%; P < 0.01). The mean age of the patients with idiopathic osteosclerosis was 31.9 ± 17.9 years and 30.8 ± 13.3 years in the patients without idiopathic osteosclerosis. The distribution of idiopathic osteosclerosis in the mandible (97.3%), mostly in the premolar region, was significantly higher than that in the maxilla (2.7%). Conclusion: Our results showed high frequencies of idiopathic osteosclerosis in Iran in comparison to some other countries. [ABSTRACT FROM AUTHOR]

The computed tomography plays an important role in the diagnosis of anomalies and pathological conditions of the TMJ, providing a complete visualization of joint region, providing a more accurate diagnosis. For evaluation of the images is necessary to the professional the knowledge of sectional anatomy of the joint region, so he can recognize the structural changes. Therefore, it was explained and described in this study the characteristics of normal CT, morphological and pathological conditions commonly found in the region of the temporomandibular joint. The Computed tomography is an imaging exam superior than the conventional imaging exam for TMJ, because it allows an adequate and accurate three-dimensional visualization of all details of the bone, without the limitation of overlap, providing the real size and shape of the anatomical structures, morphological changes and pathological conditions. [ABSTRACT FROM AUTHOR]

Mycobacterium ulcerans can lead to severe forms of infections, including osteomyelitis. This study identified patients with lesions both adjacent to and distant from skin lesions as well as those with no apparent history of skin lesions, here termed exclusive osteomyelitis.Background. Mycobacterium ulcerans is known to cause Buruli ulcer (BU), a necrotizing skin disease leading to extensive cutaneous and subcutaneous destruction and functional limitations. However, M. ulcerans infections are not limited to skin, and osteomyelitis, still poorly described in the literature, occurs in numerous young patients in Africa.Methods. In a retrospective matched case-control study conducted in a highly endemic area in Benin, we analyzed demographic, clinical, biological, and radiological features in all patients with M. ulcerans infections with bone involvement, identified from a cohort of 1257 patients with polymerase chain reaction–proved M. ulcerans infections.Results. The 81 patients studied had a median age of 11 years (interquartile range, 7–16 years) and were predominantly male (male–female ratio, 2:1). Osteomyelitis was observed beneath active BU lesions (60.5%) or at a distance from active or apparently healed BU lesions (14.8%) but also in patients without a history of BU skin lesions (24.7%). These lesions had an insidious course, with nonspecific clinical findings leading to delayed diagnosis. A comparison with findings in 243 age- and sex-matched patients with BU without osteomyelitis showed that case patients were less likely to have received BCG immunization than controls (33.3% vs 52.7%; P = .01). They were also at higher risk of longer hospital stay (118 vs 69 days; P = .001), surgery (92.6% vs 63.0%; P = .001), and long-term crippling sequelae (55.6% vs 15.2%; P < .001).Conclusions. This study highlighted the difficulties associated with diagnosis of M. ulcerans osteomyelitis, with one-fourth of patients having no apparent history of BU skin lesions, including during the current course of illness. Delays in treatment contributed to the high proportion (55.6%) of patients with crippling sequelae. [ABSTRACT FROM AUTHOR]

Case: A sixty-one-year-old woman presented with right knee pain. Imaging demonstrated osteonecrosis, pathologic fracture, and a permeative lesion. A biopsy with irrigation and debridement was performed. Cultures grew Escherichia coli, and histology showed features of malakoplakia, a rare lesion of uncertain etiology usually found in the genitourinary tract. The patient was treated successfully with antibiotics. Conclusion: Malakoplakia, although rare, should be included in the differential diagnosis of permeative bone lesions, especially in an immunocompromised patient. [ABSTRACT FROM AUTHOR]

Preterm, low-birth-weight neonates are predisposed to metabolic bone disease (MBD). This survey aimed to assess screening, diagnostic, and treatment practices in U.S. level IIIB/IIIC neonatal intensive care units (NICUs). A 29-question anonymous online survey was e-mailed to American Academy of Pediatrics Perinatal Section members. 338 neonatologists, representing 246 IIIB/IIIC NICUs, responded. 86% reported MBD screening. Screening was primarily based on gestational age (71%), with thresholds <26 to <36 weeks. Other criteria included birth weight (64%), total parenteral nutrition duration (48%), X-ray findings (56%), diuretic use (41%), and exclusive breast-feeding (9.6%). Almost universally, diagnosis was based on elevated alkaline phosphatase, most commonly >500 U/L (58.6%). 52% used X-ray for diagnosis. Treatment included human milk fortification (83%), vitamin D (67%), calcium (65%), and phosphorus (65%) supplementation. Our survey confirms widespread awareness of MBD but highlights lack of consensus regarding definition, screening, and treatment. Further research is needed to develop and optimize strategies to prevent, recognize, and manage MBD. [ABSTRACT FROM PUBLISHER]

The article discusses the research on the potential of complements C3 and C4 as biochemical markers for the diagnosis of myeloma bone disease. It mentions the findings of the research which does not find any difference in the diagnostic potential of complements, osteoblast precursors and bone formation markers. It provides a graph on the serum levels of complements C3, C4, and C4a in diagnosed multiple myeloma patients using correlation analysis.

Objectives: To investigate the angulations and length of the styloid process (SP) on three-dimensional computed tomography (3D-CT) images between the patients having elongated SP complaints and those without any stylalgia symptoms. Patients and methods: One hundred patients underwent 3D-CT evaluation of the bilateral temporomandibular joints to investigate for symptomatic elongated styloid process (ESP) at our institution. The differences between the mean angulations and lengths of the SP and comparisons between patient and control groups were analyzed by student t test. Results: In study group, mean length of styloid processes was 40.7 ± 10.8 mm on the right and 40.3 ± 10.9 mm on the left. Mean medial angles of SP were measured as 22.60 ± 4.0 on the right side and 22.60 ± 4.5 on the left side. In the same group, mean anterior angles of SP were 16.10 ± 6.9 on the right and 16.70 ± 7.1 on the left side. The 'in-group' comparisons of lengths, medial and anterior angles did not produce statistically significant results. The comparison of medial angulations between the symptomatic and asymptomatic patients was the only statistically meaningful result in our study. Conclusion: 3D-CT has several advantages according to conventional tomography for visualization of head and neck anatomy. The increase of medial angulation of SP may be responsible for the development of complaints in ESP. [ABSTRACT FROM AUTHOR]

Cortical bone is typically regarded as “MR invisible” with conventional clinical magnetic resonance imaging (MRI) pulse sequences. However, recent studies have demonstrated that free water in the microscopic pores of cortical bone has a short T2* but a relatively long T2, and may be detectable with conventional clinical spin echo (SE) or fast spin echo (FSE) sequences. In this study we describe the use of a conventional two-dimensional (2D) FSE sequence to assess cortical bone microstructure and measure cortical porosity using a clinical 3 T scanner. Twelve cadaveric human cortical bone samples were studied with MRI and microcomputed tomography (μCT) (downsampled to the same spatial resolution). Preliminary results show that FSE-determined porosity is highly correlated (R 2 = 0.83; P < 0.0001) with μCT porosity. Bland–Altman analysis suggested a good agreement between FSE and μCT with tight limit of agreement at around 3%. There is also a small bias of − 2% for the FSE data, which suggested that the FSE approach slightly underestimated μCT porosity. The results demonstrate that cortical porosity can be directly assessed using conventional clinical FSE sequences. The clinical feasibility of this approach was also demonstrated on six healthy volunteers using 2D FSE sequences as well as 2D ultrashort echo time (UTE) sequences with a minimal echo time (TE) of 8 μs, which provide high contrast imaging of cortical bone in vivo. [ABSTRACT FROM AUTHOR]

Objective: To determine the rates of diagnostic success and complications of computed tomography (CT)-guided percutaneous biopsy of bone lesions suspected for malignancy. Materials and Methods: Retrospective study including 186 cases of CT-guided percutaneous biopsies of bone lesions in the period from January, 2010 to December, 2012. All the specimens were obtained with 8–10 gauge needles. The following data were collected: demographics, previous history of malignancy, data related to the lesion, to the procedure, and to histological results. Results: Most patients were women (57%), and the mean age was 53.0 ± 16.4 years. In 139 cases (74.6%), there was diagnostic suspicion of metastasis and the most common primary tumors were breast (32.1%) and prostate (11.8%). The bones most commonly involved were spine (36.0%), hip (32.8%) and long bones (18.3%). Complications occurred in only three cases (1.6%) including bone fracture, paresthesia with functional impairment, and needle breakage requiring surgical removal. The specimens collected from 183 lesions (98.4%) were considered appropriate for diagnosis. Malignant results were more frequently found in patients who had a suspected secondary lesion and history of known malignancy (p < 0.001), and in patients who underwent PET/CT-guided procedures (p = 0.011). Conclusion: CT-guided percutaneous biopsy is a safe and effective procedure for the diagnosis of suspicious bone lesions. [ABSTRACT FROM AUTHOR]

Aims Diabetic foot osteomyelitis is an important risk factor of lower limb amputation. Antibiotic therapy is often effective in preventing surgery. However, the duration of antibiotic therapy is difficult to define in the absence of a marker to diagnose osteomyelitis remission at the end of the treatment. In this study, we assessed the diagnostic performance of white blood cell SPECT/CT imaging for evaluating osteomyelitis remission. Patients and methods Twenty-nine out of 42 episodes of diabetic foot osteomyelitis seen between December 2009 and April 2012 had radiographs, a three-phase bone scintigraphy and a white blood cell SPECT/CT at the end of antibiotic therapy. They were treated with antibiotics alone and considered in clinical remission. White blood cell SPECT/CT results were considered positive when abnormal uptake in the osteomyelitis location was identified. Osteomyelitis remission was defined by the absence of an osteomyelitis relapse after 12 months' follow-up. Results A negative white blood cell SPECT/CT was seen for 22 episodes of osteomyelitis. All of them were in remission. A positive white blood cell SPECT/CT was observed for seven episodes. A relapse occurred in five episodes (71.5%) after a median duration of 4 months (2-7 months). Sensitivity, specificity, positive predictive value and predictive negative value in predicting osteomyelitis relapse after the discontinuation of antibiotic treatment were, respectively, for radiographs 80%, 33%, 20% and 89%; for three-phase bone scintigraphy 100%, 12.5%, 15.5% and 100%; and for the white blood cell SPECT/CT 100%, 91.5%, 71.5% and 100%. Conclusion Negative uptake on white blood cell SPECT/CT is a good marker for diagnosis of diabetic foot osteomyelitis remission and might be very useful in guiding antibiotic therapy. [ABSTRACT FROM AUTHOR]

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The diagnosis of anaerobic bone and joint infections (BJI) were underestimated before the advent of molecular identification and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). We report 61 cases of anaerobic infections based on our 4-year experience with the management of BJI. A total of 75 % of cases were post-surgical infections, associated with osteosynthesis devices (65 %). Early infections occurred in 27 % of cases, delayed infections in 17.5 % of cases, and late infections in 55 % of cases. We recorded 36 species of 93 anaerobic strains using MALDI-TOF MS (91) and molecular methods (2). We identified 20 strains of Propionibacterium acnes, 13 of Finegoldia magna, six of Peptoniphilus asaccharolyticus, and six of P. harei. Polymicrobial infections occurred in 50 cases. Surgical treatment was performed in 93.5 % of cases. The antibiotic treatments included amoxicillin (30 %), amoxicillin-clavulanic acid (16 %), metronidazole (30 %), and clindamycin (26 %). Hyperbaric oxygen therapy was used in 17 cases (28 %). The relapse rate (27 %) was associated with lower limbs localization ( p = 0.001). P. acnes BJI was associated with shoulder ( p = 0.019), vertebra ( p = 0.021), and head flap localization ( p = 0.011), and none of these cases relapsed ( p = 0.007). F. magna BJI was associated with ankle localization ( p = 0.014). Anaerobic BJI is typically considered as a post-surgical polymicrobial infection, and the management of this infection combines surgical and medical treatments. MALDI-TOF MS and molecular identification have improved diagnosis. Thus, physicians should be aware of the polymicrobial nature of anaerobic BJI to establish immediate broad-spectrum antibiotic treatment during the post-surgical period until accurate microbiological results have been obtained. [ABSTRACT FROM AUTHOR]

Background: Recently, computed tomography (CT) has been used to diagnose fetal skeletal dysplasia. However, no surveys have been conducted to determine the radiation exposure dose and the diagnostic reference level (DRL). Objective: To collect CT dose index volume (CTDIvol) and dose length product (DLP) data from domestic hospitals implementing fetal skeletal 3-D CT and to establish DRLs for Japan. Materials and methods: Scan data of 125 cases of 20 protocols from 16 hospitals were analyzed. The minimum, first-quartile, median, third-quartile and maximum values of CTDIvol and DLP were determined. The time-dependent change in radiation dose setting in hospitals with three or more cases with scans was also examined. Results: The minimum, first-quartile, median, third-quartile and maximum CTDIvol values were 2.1, 3.7, 7.7, 11.3 and 23.1 mGy, respectively, and these values for DLP were 69.0, 122.3, 276.8, 382.6 and 1025.6 mGy·cm, respectively. Six of the 12 institutions reduced the dose setting during the implementation period. Conclusions: The DRLs of CTDIvol and DLP for fetal CT were 11.3 mGy and 382.6 mGy·cm, respectively. Institutions implementing fetal CT should use these established DRLs as the standard and make an effort to reduce radiation exposure by voluntarily decreasing the dose. [ABSTRACT FROM AUTHOR]

Abstract: Osteoporosis is the most common bone disease with severe symptoms and harmful effects on the patient quality of life. Because abnormal distribution and concentration of the major and trace elements may help to characterize the disease, ion beam analysis is applied to the study of bone samples. Proton Induced X-ray Emission and Elastic Backscattering Spectrometry are applied for qualitative and quantitative analysis of an osteoporotic bone sample, for the determination of the Ca/P ratio and analysis of the distribution of major and trace elements. The analysis was made both in trabecular and cortical bone and the results are in agreement with the information found in literature. [Copyright &y& Elsevier]

Objective: Few imaging studies have investigated cartilage in gout. Magnetic resonance imaging (MRI) can image cartilage damage and also reveals other features of gouty arthropathy. The objective was to develop and validate a system for quantifying cartilage damage in gout. Methods: 3-T MRI scans of the wrist were obtained in 40 gout patients. MRI cartilage damage was quantified using an adaptation of the radiographic Sharp van der Heijde score. Two readers scored cartilage loss at 7 wrist joints: 0 (normal), 1 (partial narrowing), 2 (complete narrowing) and concomitant osteoarthritis was recorded. Bone erosion, bone oedema and synovitis were scored (RAMRIS) and tophi were assessed. Correlations between radiographic and MRI cartilage scores were investigated, as was the reliability of the MRI cartilage score and its associations. Results: The GOut MRI Cartilage Score (GOMRICS) was highly correlated with the total Sharp van der Heijde (SvdH) score and the joint space narrowing component (R = 0.8 and 0.71 respectively, p < 0.001). Reliability was high (intraobserver, interobserver ICCs = 0.87 [0.57-0.97], 0.64 [0.41-0.79] respectively), and improved on unenhanced scans; interobserver ICC = 0.82 [0.49-0.95]. Cartilage damage was predominantly focal (82 % of lesions) and identified in 40 out of 280 (14 %) of joints. Cartilage scores correlated with bone erosion (R = 0.57), tophus size (R = 0.52), and synovitis (R = 0.55), but not bone oedema scores. Conclusions: Magnetic resonance imaging can be used to investigate cartilage in gout. Cartilage damage was relatively uncommon, focal, and associated with bone erosions, tophi and synovitis, but not bone oedema. This emphasises the unique pathophysiology of gout. [ABSTRACT FROM AUTHOR]

Background and purpose: Schnitzler syndrome is characterized by chronic urticaria, monoclonal gammopathy, and a risk of developing lymphoproliferative disorders. Patients frequently present with bone pain, fever, arthralgia, and lymphadenopathy. The purpose of this study is to retrospectively review and evaluate potentially attributable imaging abnormalities in a series of patients with clinically diagnosed Schnitzler syndrome. Materials and methods: Clinical and pathological chart review identified 22 patients meeting Strasbourg criteria for Schnitzler syndrome. Imaging of these patients was retrospectively reviewed by a musculoskeletal radiologist and a radiology fellow to determine and characterize significant 'positive' findings that could potentially be attributed to their primary disease process. Results: Evidence of abnormal bone remodeling was present in 64 % (14/22) of patients with 40 bone abnormalities. Lesions were predominantly or entirely sclerotic and most commonly involved the distal femora ( n = 11), proximal tibiae (nine), and innominate bones (six). Patterns of involvement were variable, but typically eccentrically intramedullary, cortical, and juxta-articular. Skeletal surveys and targeted radiographs identified only 37 % (10/27) of abnormal bones subsequently 'positive' by additional modalities. PET and bone scans were all positive in patients with bone sclerosis (13/13 and 17/17 bone sites, respectively). Conclusions: Schnitzler syndrome often presents with characteristic osteosclerosis, most commonly around the knees and in the pelvis. In patients with a suggestive clinical history, the radiologist could direct an appropriate imaging strategy or might to be the first to suggest the diagnosis. Bone scan may be the most appropriate initial screening tool in suspected cases. [ABSTRACT FROM AUTHOR]