Molecular alterations of bone quality in sequesters of bisphosphonates-related osteonecrosis of the jaws.

UNLABELLED: Compared to healthy bone, the intrinsic bone materials properties in the pre-existing lamellar bone are altered in jaw bone sequesters of bisphosphonates (BP)-related osteonecrosis. INTRODUCTION: The aim of this study was to evaluate the human jaw bone quality, especially intrinsic bone material properties among sequesters of osteonecrosis of the jaw (ONJ) induced by BP. METHODS: Bone sequesters were obtained from 24 patients suffering from ONJ following a BP treatment. Within BP-exposed bone samples, benign-BP and malignant-BP groups were distinguished in relation to the underlying disease: osteoporosis and bone metastases or multiple myeloma, respectively. Healthy cadaveric cortical jaw bone samples were used as controls. The physicochemical parameters of bone samples - mineral/organic ratio, relative proteoglycan content, crystallinity, monohydrogen phosphate content, and type-B carbonate substitution - were evaluated by Raman microspectroscopy. Representative Raman spectral features of bones control and BP-exposed bone sequesters were identified with the Partial-Least-Square Discriminant Analysis (PLS-DA). RESULTS: BP-exposed bone sequesters are characterized by a significant increase of mineral to organic ratio (+12 %) and a significant decrease of relative proteoglycan content (-35 %), thus regulating initial collagen matrix mineral deposition. Structural changes on mineral components are revealed by a significant decrease of both crystallinity (-2 %) and mineral maturation (-41 %) in the BP-exposed bone sequesters compared to healthy bones. These modifications were also observed distinctly in both benign-BP and malignant-BP groups. In addition, a shift of the phosphate ν1 band was highlighted by PLS-DA between bones control and BP-exposed bone sequesters, revealing a disruption of the apatitic phosphate environment in the jaw bone sequesters. CONCLUSIONS: The present data show that jaw bone quality can be altered with an overmineralization and ultrastructural modifications of apatitic mineral in bone sequesters of BP-related ONJ.

Clinical relevance of spectral tissue Doppler-derived E/e' in older patients with preserved ejection fraction.

BACKGROUND: The E/e' index measured in spectral tissue Doppler is included in the recommendations for the diagnosis by transthoracic Doppler echocardiography of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction. While E/e' is influenced by age in healthy individuals, no studies have evaluated this index in elderly patients. This study addressed the clinical relevance of E/e' in assessment of left ventricular diastolic function in elderly patients with preserved ejection fraction and its relevance from both a diagnostic and prognostic perspective based on the existing literature. METHODS: A total of 76 patients≥70years of age were prospectively included. The analysis of left ventricular diastolic function was adapted from the 2016 ASE/EACVI recommendations without consideration of E/e'. RESULTS: The mean age was 85years. In all, 42 patients had moderate-to-severe diastolic dysfunction (elevated left atrial pressure). Mean E/e' was significantly correlated with diastolic function (r=0.58, P<0.001). Mean E/e'>13.3 had a sensitivity of 86% and a specificity of 91% in the diagnosis of moderate-to-severe diastolic dysfunction (AUC: 0.92). E/(e'xs') (AUC: 0.89) and NT pro-BNP (AUC: 0.80) did not perform better than E/e'. The existing literature offers large body of evidence that E/e' provides essential diagnostic and prognostic information in older patients with cardiovascular disease. CONCLUSION: E/e' is accurate in the diagnosis of significant diastolic dysfunction, in the diagnosis of heart failure with preserved ejection fraction and in risk stratification in older patients with cardiovascular disease.

Effects of high dose of zoledronic acid on superficial vascular network of membranous bone sites: an intravital study on rat calvarium.

UNLABELLED: We evaluated the impact of high dose of zoledronic acid on the superficial vascular network parameters of a membranous bone site. During a 5-day follow-up, significant reduction of the vascular density is observed only in the treated group. INTRODUCTION: The superficial vascularization is of great importance in membranous bone-healing process. A new rat calvarium intravital model was developed to study the short-term effect of a single high dose of zoledronic acid infusion on the superficial vascularization. METHODS: Optical bone chambers were implanted in the bone tissue surface of Sprague-Dawley rats' calvarium. Nine rats were injected i.v. with 400 µg/kg of zoledronic acid (Z group), and nine rats were injected with vehicle (PSS group). A 5-day follow-up of the vascular network was made by the use of pictures analysis method. RESULTS: The vascular density significantly decreases only in Z group but there was no significant difference between groups at individual time points. The total length of the vascular network decreases significantly in Z group only (p=0.003) with a significant higher decrease at D3 (p=0.04) and D5 (p=0.02) compared with control. The vascular density related to the smaller vessels (width, 5-10 µm) decreases significantly between T0 and D5 in Z group only (p=0.002). CONCLUSIONS: With the help of an original intravital animal model a significant modifications on the total length of the vascular network and the vascular density of small vessels are highlighted on a membranous bone site.

[Radiotherapy of bone metastases]. / Radiothérapie des métastases osseuses.

Radiotherapy plays a major role in palliative treatment of bone metastases. Recent developments of stereotactic radiotherapy and intensity modulated radiation therapy give the possibility to treat oligometastatic diseases. The objective of this paper is to report indications and treatment modalities of radiotherapy in these situations.

[Spondylodiscitis due to Salmonella enteritica serotype Typhi]. / Spondylodiscite à Salmonella enteritica sérotype Typhi.

We reported a case of lombar spondylodiscitis caused by Salmonella enteritica serotype Typhi in an immunocompetent patient. Salmonella is a rare causative agent of spondylodiscitis. Early bacteriological diagnosis is essential to avoid longterm sequelae.

[Hemolytic anemia due to naphthalene poisoning]. / Anémie hémolytique par intoxication à la naphtaline.

INTRODUCTION: Naphthalene ingestion is a rare cause of hemolysis. CASE REPORT: We report a 33-year-old woman, originating from the Comoros, hospitalized for intense fatigue associated with delirium, fever and jaundice, three days after ritual ingestion of naphthalene. Biochemical parameters showed marked hemolysis. Outcome was favorable after red cells transfusion and hydratation with intravenous fluids. CONCLUSION: Diagnostic work-up of unexplained hemolysis should include the search for toxic exposition. Naphthalene poisoning can present with diagnostic challenge for physicians.

No anti-angiogenic effect of clinical dosing regimens of a single zoledronic acid injection in an experimental bone healing site.

INTRODUCTION: An anti-angiogenic effect of bisphosphonates has been reported in different experimental models. Zoledronic acid is currently administered in osteoporotic patients as a single 5 mg injection once a year and its vascular effect in bone has not been yet evaluated. MATERIALS AND METHODS: The vascular dose effect of a single injection of zoledronic acid was evaluated on healing vascularization developed under a bone chamber implanted on the calvaria of 30 rats. After 3 weeks of healing, the rats were randomized into 3 groups receiving an injection of either physiologic saline solution (PSS) or zoledronic acid tested at 120 microg/kg, the equivalent of a 5 mg dose of zoledronic acid in humans (Z120), and 400 microg/kg, a supra-pharmacologic dose (Z400). A longitudinal follow-up of the healing vascular network was carried out at days (D) 1, 3, 6, 9, 12, 15 and 28 after injection by intravital imaging. Variations in vascular density, total length of the vascular network and mean diameter of vascular network branches were determined by image analysis (Aphelion software). RESULTS: A decrease was observed in both vascular density and total length of the network in control and treated groups (time effect). No difference in variation in vascular density was observed between the PSS group and the Z120 group at any time point (p=NS). A trend to a higher decrease in vascular density was noted between D12 and D15 in the Z400 group. A significant decrease in total length was noted at D15 in the Z400 group (p=0.03) compared to the PSS group, whereas no change was noted in rats treated with 120 microg/kg compared to PSS rats on any of the follow-up days (p=0.2). No variation in mean diameter of vascular network branches was noted in any of the three groups at any of the follow-up days (p=0.53). CONCLUSION: A single injection of clinically relevant dosing regimens of zoledronic acid may not have a notable impact on vascularization in bone sites. The anti-angiogenic effect of bisphosphonates seems to express itself, in our model, at higher doses than those used in patients treated for osteoporosis.