Differences in bone microarchitecture between genetic and secondary iron-overload mouse models suggest a role for hepcidin deficiency in iron-related osteoporosis.

Iron overload is one of the secondary osteoporosis etiologies. Cellular and molecular mechanisms involved in iron-related osteoporosis are not fully understood. AIM: The aim of the study was to investigate the respective roles of iron excess and hepcidin, the systemic iron regulator, in the development of iron-related osteoporosis. MATERIAL AND METHODS: We used mice models with genetic iron overload (GIO) related to hepcidin deficiency (Hfe-/- and Bmp6-/- ) and secondary iron overload (SIO) exhibiting a hepcidin increase secondary to iron excess. Iron concentration and transferrin saturation levels were evaluated in serum and hepatic, spleen, and bone iron concentrations were assessed by ICP-MS and Perl's staining. Gene expression was evaluated by quantitative RT-PCR. Bone micro-architecture was evaluated by micro-CT. The osteoblastic MC3T3 murine cells that are able to mineralize were exposed to iron and/or hepcidin. RESULTS: Despite an increase of bone iron concentration in all overloaded mice models, bone volume/total volume (BV/TV) and trabecular thickness (Tb.Th) only decreased significantly in GIO, at 12 months for Hfe-/- and from 6 months for Bmp6-/- . Alterations in bone microarchitecture in the Bmp6-/- model were positively correlated with hepcidin levels (BV/TV (ρ = +.481, p < .05) and Tb.Th (ρ = +.690, p < .05). Iron deposits were detected in the bone trabeculae of Hfe-/- and Bmp6-/- mice, while iron deposits were mainly visible in bone marrow macrophages in secondary iron overload. In cell cultures, ferric ammonium citrate exposure abolished the mineralization process for concentrations above 5 µM, with a parallel decrease in osteocalcin, collagen 1, and alkaline phosphatase mRNA levels. Hepcidin supplementation of cells had a rescue effect on the collagen 1 and alkaline phosphatase expression level decrease. CONCLUSION: Together, these data suggest that iron in excess alone is not sufficient to induce osteoporosis and that low hepcidin levels also contribute to the development of osteoporosis.

Oxidative and glycolytic skeletal muscles deploy protective mechanisms to avoid atrophy under pathophysiological iron overload.

BACKGROUND: Iron excess has been proposed as an essential factor in skeletal muscle wasting. Studies have reported correlations between muscle iron accumulation and atrophy, either through ageing or by using experimental models of secondary iron overload. However, iron treatments performed in most of these studies induced an extra-pathophysiological iron overload, more representative of intoxication or poisoning. The main objective of this study was to determine the impact of iron excess closer to pathophysiological conditions on structural and metabolic adaptations (i) in differentiated myotubes and (ii) in skeletal muscle exhibiting oxidative (i.e. the soleus) or glycolytic (i.e. the gastrocnemius) metabolic phenotypes. METHODS: The impact of iron excess was assessed in both in vitro and in vivo models. Murine differentiated myotubes were exposed to ferric ammonium citrate (FAC) (i.e. 10 and 50 µM) for the in vitro component. The in vivo model was achieved by a single iron dextran subcutaneous injection (1 g/kg) in mice. Four months after the injection, soleus and gastrocnemius muscles were harvested for analysis. RESULTS: In vitro, iron exposure caused dose-dependent increases of iron storage protein ferritin (P < 0.01) and dose-dependent decreases of mRNA TfR1 levels (P < 0.001), which support cellular adaptations to iron excess. Extra-physiological iron treatment (50 µM FAC) promoted myotube atrophy (P = 0.018), whereas myotube size remained unchanged under pathophysiological treatment (10 µM FAC). FAC treatments, whatever the doses tested, did not affect the expression of proteolytic markers (i.e. NF-κB, MurF1, and ubiquitinated proteins). In vivo, basal iron content and mRNA TfR1 levels were significantly higher in the soleus compared with the gastrocnemius (+130% and +127%; P < 0.001, respectively), supporting higher iron needs in oxidative skeletal muscle. Iron supplementation induced muscle iron accumulation in the soleus and gastrocnemius muscles (+79%, P < 0.001 and +34%, P = 0.002, respectively), but ferritin protein expression only increased in the gastrocnemius (+36%, P = 0.06). Despite iron accumulation, muscle weight, fibre diameter, and myosin heavy chain distribution remained unchanged in either skeletal muscle. CONCLUSIONS: Together, these data support that under pathophysiological conditions, skeletal muscle can protect itself from the related deleterious effects of excess iron.

Calcium pyrophosphate deposition (CPPD) in a liver transplant patient: are hypomagnesemia, tacrolimus or both guilty? A case-based literature review.

Calcium pyrophosphate deposition (CPPD) can be induced by a persistent hypomagnesemia. Tacrolimus is an immunosuppressive treatment especially used in organ transplant, potentially inducer of hypomagnesemia by renal loss. A 53-year-old man, liver transplant 10 months earlier, developed an acute peripheral oligoarthritis of wrist, hip and elbow with fever, associated with acute low back pain. Synovial fluid was sterile, and revealed calcium pyrophosphate crystals. Spinal imaging showed inflammatory changes. Magnesium blood level was low at 0.51 mmol/l, with high fractional excretion in favor of renal loss. Tacrolimus was changed for everolimus, proton pump inhibitor was stopped, and magnesium oral supplementation was started. After 8 months follow-up and slow prednisone tapering, he did not relapse pain. Persistent hypomagnesemia is a rare secondary cause of CPPD. In this entity, drug liability should be investigated such as tacrolimus in organ transplant patient.

Denosumab in the management of Aneurysmal bone cyst.

BACKGROUND: Aneurysmal bone cyst (ABC) is a benign, locally aggressive tumour that arises predominantly in long bones and spine. Following the encouraging results of denosumab use in Giant Cell Tumors (GCT) and the histological similarities between ABC and GCT, the interest on the role of denosumab in the therapeutic arsenal of the most advanced ABC is growing. The purpose of this literature review is to investigate the current state of knowledge about the use of denosumab in ABCs. METHODS: A literature research was conducted through PUBMED, COCHRANE and GOOGLE SCHOLAR using the keywords "aneurysmal bone cyst" AND "denosumab". Seventeen articles were included. RESULTS: A total of 43 cases were reported in the literature. There were 23 males, 20 females. The mean age was 15,9±8,1 year. Pain relief and neurological improvement were rapid and sustained. Radiological assessment showed ossification and/or volume reduction in 36/39 patients. Eight patients (18,6%) presented a recurrence after or during denosumab therapy of whom 7 were adults. Adverse events occurred in 11 patients, 5 of them were admitted to the intensive care unit due to hypercalcemia. CONCLUSION: Denosumab use in non-surgical ABCs has shown a positive impact in pain and neurological symptoms. The oncological outcome remains unclear with a recurrence rate of 18,6% during/after denosumab therapy, mostly in adults. However, regarding the potential clinical benefits, its use might be discussed in the most advanced cases. Further research and clinical trials are mandatory to precise its belonging in the therapeutic arsenal.

Surgical management of MILD hyperparathyroidism.

INTRODUCTION: There is no consensus for management of Mild primary hyperparathyroidism (MILD-pHP). Specific management has been suggested by some authors. We have compared the surgical management of the patients with MILD-pHP to those with Classic primary hyperparathyroidism (C-pHP) treated by surgery according to The Fourth International Workshop on pHP. MATERIALS AND METHODS: Data of 173 patients who underwent a parathyroidectomy were reviewed and retrospectively analysed. Management of 32 patients with MILD-pHPT (18.5%) patients were compared to that of 141 (81.5%) patients with C-pHPT. RESULTS: MILD-pHP group was more often discovered after non-fractured osteoporosis (21.9% vs 7.1%, p = 0.02) and surgery for chondrocalcinosis was more often carried out (6.3% vs 0%, p = 0.03) in the MILD-pHP group. A Mini-Invasive Parathyroidectomy (MIP) was carried out in 81.3% of cases, and 87.5% of patients had a single adenoma. The rate of multiglandular pathology was not different. Same day discharge was significantly higher in MILD-pHP group (37.5% vs 17.7%, p = 0.01). Success was obtained in 87.5% in the MILD-pHP group, there was no significant difference with the C-pHP group (92.9%, p = 0.48). There was no significant difference in the imaging performances. Imaging discordance was observed in 18.8% of cases in MILD-pHP and 33.6% in C-pHP (p = 0.38) without correlation with surgical failure. CONCLUSION: This study suggests that, by selecting patients on the basis of concordant imaging and international recommendations, there is no difference in outcome between MILD-pHP and C-pHP treated surgically.

2020 French recommendations on the management of septic arthritis in an adult native joint.

Septic arthritis (SA) in an adult native joint is a rare condition but a diagnostic emergency due to the morbidity and mortality and the functional risk related to structural damage. Current management varies and the recommendations available are dated. The French Rheumatology Society (SFR) Bone and Joint Infection Working Group, together with the French Language Infectious Diseases Society (SPILF) and the French Orthopaedic and Trauma Surgery Society (SOFCOT) have worked according to the HAS methodology to devise clinical practice recommendations to diagnose and treat SA in an adult native joint. One new focus is on the importance of microbiological documentation (blood cultures and joint aspiration) before starting antibiotic treatment, looking for differential diagnoses (microcrystal detection), the relevance of a joint ultrasound to guide aspiration, and the indication to perform a reference X-ray. A cardiac ultrasound is indicated only in cases of SA involving Staphylococcus aureus, oral streptococci, Streptococcus gallolyticus or Enterococcus faecalis, or when infective endocarditis is clinically suspected. Regarding treatment, we stress the importance of medical and surgical collaboration. Antibiotic therapies (drugs and durations) are presented in the form of didactic tables according to the main bacteria in question (staphylococci, streptococci and gram-negative rods). Probabilistic antibiotic therapy should only be used for patients with serious symptoms. Lastly, non-drug treatments such as joint drainage and early physical therapy are the subject of specific recommendations.

Spondyloarthritis and sarcoidosis: Related or fake friends? A systematic literature review.

BACKGROUND: Sarcoidosis and spondyloarthritis (SpA) have been regularly associated. Bone iliac granulomas have also been described. We propose herein a systematic review of rheumatologic axial manifestations of sarcoidosis. METHODS: PubMed and the Cochrane Library were used to conduct this systematic literature review. Case reports and cross-sectional studies were reviewed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 41 articles were eligible. Three cross-sectional studies on the association between SpA and sarcoidosis showed a prevalence of sacroiliitis and SpA ranging from 12.9 to 44.8% and 12.9 to 48.3% in inflammatory back pain (IBP) subgroups, respectively. However, the IBP definitions and sacroiliac joint (SIJ) imaging modalities (X-rays or magnetic resonance imaging) were heterogeneous, and X-ray was mainly used for sacroiliitis diagnosis (in 78% of cases). Thirty-one case-report articles of the sarcoidosis-sacroiliitis association were identified, representing 35 patients. ASAS criteria for SpA were met in half of cases (16/32) and 46% (12/26) had HLA B27 positivity. Sarcoidosis occurred after sacroiliac symptoms in 47% of cases. In the seven case-report articles with granulomatous sacroiliac bone involvement, unilateral involvement seemed higher than in the sarcoidosis-sacroiliitis group. CONCLUSION: Literature analysis found a good evidence of the association between SpA and sarcoidosis, and special attention should be given to patients reporting IBP. Unilateral sacroiliitis may raise suspicion of granulomatous bone involvement, distinct from sacroiliitis. Imaging modalities used to study the SIJ in patients with sarcoidosis have been heterogeneous and further investigation is needed.

Spleen iron, molybdenum, and manganese concentrations are coregulated in hepcidin-deficient and secondary iron overload models in mice.

Iron excess increases the hepatic expression of hepcidin, the systemic iron metabolism regulator that favors iron sequestration in the spleen. Genetic iron overload related to hepcidin insufficiency decreases the spleen iron concentration and increases hepatic iron concentration, whereas during secondary iron overload, the hepcidin expression increases together with spleen iron concentration in addition to hepatic iron concentrations increase. Links between iron metabolism and other metals being suggested, our aim was to investigate, during iron overload, the relationships between the hepatic hepcidin expression level and the hepatic and splenic concentrations of iron, manganese, copper, zinc, and molybdenum, determined using inductively coupled plasma mass spectrometry. Hepcidin-deficient mice, secondary iron overload mice models, and their respective controls were studied. Spleen molybdenum and manganese concentrations paralleled the modulation of both spleen iron concentrations, increasing in secondary iron overload and decreasing in hepcidin deficiency related iron overload, as well as hepatic hepcidin mRNA expression. Our data suggest that iron, manganese, and molybdenum metabolisms could share mechanisms controlling their distribution that are associated to hepcidin modulation. In diseases with abnormal hepcidin levels, including chronic inflammation, special attention should be paid to those metals that can participate with the phenotype.-Cavey, T., Latour, C., Island, M.-L., Leroyer, P., Guggenbuhl, P., Coppin, H., Roth, M.-P., Bendavid, C., Brissot, P., Ropert, M., Loréal, O. Spleen iron, molybdenum, and manganese concentrations are coregulated in hepcidin-deficient and secondary iron overload models in mice.

Back pain following instillations of BCG for superficial bladder cancer is not a reactive complication: review of 30 Mycobacterium bovis BCG vertebral osteomyelitis cases.

Mycobacterium bovis Bacillus Calmette-Guérin (BCG) instillations are used in bladder cancer treatment. Adverse effects can occur. Osteoarticular complications are mainly reactive arthritis, but true infections have been described, such as vertebral osteomyelitis. We made a review of M. bovis BCG vertebral osteomyelitis after instillations for bladder cancer using PubMed search. We added three new French cases. Twenty-seven cases of BCG vertebral osteomyelitis had been reported on PubMed. Of the 30 cases, all were male, averaging 73.4 ± 8.7 years old. Median time between diagnosis and first and last instillation was 22.5 and 14 months respectively. Half of vertebral osteomyelitis was thoracic and lumbar in the other half. Sensitivo-motor deficit was present at diagnosis in 42% of cases. Other infectious locations were common, mainly infectious abdominal aortic aneurysms (20%). Rifampicin, ethambutol and isoniazid were the usual therapy. Poor outcomes were reported with 50% of one or more spine surgery. M. bovis BCG vertebral osteomyelitis following bladder instillation for bladder cancer is a rare complication. However, the late onset of back pain after instillations differentiates them from reactive arthritis. Concomitant septic location such as infectious abdominal aortic aneurysms must be known.

Iron as a Therapeutic Target in HFE-Related Hemochromatosis: Usual and Novel Aspects.

Genetic hemochromatosis is an iron overload disease that is mainly related to the C282Y mutation in the HFE gene. This gene controls the expression of hepcidin, a peptide secreted in plasma by the liver and regulates systemic iron distribution. Homozygous C282Y mutation induces hepcidin deficiency, leading to increased circulating transferrin saturation, and ultimately, iron accumulation in organs such as the liver, pancreas, heart, and bone. Iron in excess may induce or favor the development of complications such as cirrhosis, liver cancer, diabetes, heart failure, hypogonadism, but also complaints such as asthenia and disabling arthritis. Iron depletive treatment mainly consists of venesections that permit the removal of iron contained in red blood cells and the subsequent mobilization of stored iron in order to synthesize hemoglobin for new erythrocytes. It is highly efficient in removing excess iron and preventing most of the complications associated with excess iron in the body. However, this treatment does not target the biological mechanisms involved in the iron metabolism disturbance. New treatments based on the increase of hepcidin levels, by using hepcidin mimetics or inducers, or inhibitors of the iron export activity of ferroportin protein that is the target of hepcidin, if devoid of significant secondary effects, should be useful to better control iron parameters and symptoms, such as arthritis.

Ultrasound-guided synovial biopsy improves diagnosis of septic arthritis in acute arthritis without enough analyzable synovial fluid: a retrospective analysis of 176 arthritis from a French rheumatology department.

To assess the diagnostic value of ultrasound-guided (US-guided) synovial biopsy in routine clinical practice in cases of acute and chronic arthritis. A retrospective, single-center study of US-guided synovial biopsies between 2003 and 2013. The clinical, laboratory, radiographic, synovial fluid, and histological and bacteriological results of synovial biopsies were analyzed. Arthritis was classified according to disease duration < 6 weeks (AA) or ≥ 6 weeks (CA). Synovial biopsy success rate was defined by the rate of capsular and/or synovial tissue analyzed. The diagnostic efficiency was defined by synovial biopsy success rate multiplied by the clinical utility (validation of a diagnostic hypothesis leading to a specific therapy). One hundred seventy-six US-guided synovial biopsies (51 AA and 125 CA) were analyzed. Synovial biopsy success rate was 82.4%. The diagnostic efficiency was 19.9%. Among the acute arthritis cases, 11 were septic. Only three patients had a positive biopsy culture while the synovial fluid puncture was of insufficient quantity to allow bacteriological analysis. The perivascular infiltration of neutrophils (PMN) had a sensitivity of 81.8%, a specificity of 84.2%, and a positive likelihood ratio of 5.2 for the septic arthritis diagnosis. Among the chronic arthritis cases, no case of pyogenic septic arthritis was found. No histological lesions, examined separately, were specific to a type of chronic inflammatory joint disease. US-guided synovial biopsies remain relevant for the diagnosis of septic arthritis, in cases of acute arthritis when joint aspiration is not possible.

High bone mass in adults.

A finding of high bone mineral density (BMD) from routine dual-energy X-ray absorptiometry (DXA) screening is not uncommon. No consensus exists about the definition of high BMD, and T-score and/or Z-score cutoffs of ≥+2.5 or ≥+4 have been suggested. The many disorders that can result in high BMD are usually classified based on whether the BMD changes are focal vs. generalized or acquired vs. constitutional. In over half the cases, careful interpretation of the DXA report and images identifies the cause as an artefact (e.g., degenerative spinal disease, vascular calcifications, or syndesmophytes) or focal lesion (e.g., sclerotic bone metastasis or Paget's disease). Generalized acquired high BMD may be secondary to a diverse range of disorders such as fluorosis, diffuse bone sclerosis related to renal osteodystrophy, hematological diseases, and hepatitis C. Identification of the cause may require additional investigations such as imaging studies, serum tryptase assay, or serological tests for the hepatitis C virus. Finally, high BMD is a feature of many genetic diseases, most notably osteopetrosis and the disorders caused by mutations in the sclerostin gene SOST (sclerosing bone dysplasia and van Buchem disease) or in the LRP5 gene encoding the low-density lipoprotein receptor-related protein 5 (which is the Wnt co-receptor).

Genetic analysis of adults heterozygous for ALPL mutations.

Hypophosphatasia (HPP) is a rare inherited metabolic bone disease due to a deficiency of the tissue nonspecific alkaline phosphatase isoenzyme (TNSALP) encoded by the ALPL gene. Patients have consistently low serum alkaline phosphatase (AP), so that this parameter is a good hallmark of the disease. Adult HPP is heterogeneous, and some patients present only mild nonpathognomonic symptoms which are also common in the general population such as joint pain, osteomalacia and osteopenia, chondrocalcinosis, arthropathy and musculoskeletal pain. Adult HPP may be recessively or dominantly inherited; the latter case is assumed to be due to the dominant negative effect (DNE) of missense mutations derived from the functional homodimeric structure of TNSALP. However, there is no biological argument excluding the possibility of other causes of dominant HPP. Rheumatologists and endocrinologists are increasingly solicited for patients with low AP and nonpathognomonic symptoms of HPP. Many of these patients are heterozygous for an ALPL mutation and a challenging question is to determine if these symptoms, which are also common in the general population, are attributable to their heterozygous ALPL mutation or not. In an attempt to address this question, we reviewed a cohort of 61 adult patients heterozygous for an ALPL mutation. Mutations were distinguished according to their statistical likelihood to show a DNE. One-half of the patients carried mutations predicted with no DNE and were slightly less severely affected by the age of onset, serum AP activity and history of fractures. We hypothesized that these mutations result in another mechanism of dominance or are recessive alleles. To identify other genetic factors that could trigger the disease phenotype in heterozygotes for potential recessive mutations, we examined the next-generation sequencing results of 32 of these patients for a panel of 12 genes involved in the differential diagnosis of HPP or candidate modifier genes of HPP. The heterozygous genotype G/C of the COL1A2 coding SNP rs42524 c.1645C > G (p.Pro549Ala) was associated with the severity of the phenotype in patients carrying mutations with a DNE whereas the homozygous genotype G/G was over-represented in patients carrying mutations without a DNE, suggesting a possible role of this variant in the disease phenotype. These preliminary results support COL1A2 as a modifier gene of HPP and suggest that a significant proportion of adult heterozygotes for ALPL mutations may have unspecific symptoms not attributable to their heterozygosity.

Atypical presentation of spine bone metastasis in prostate cancer mimicking Pott's disease.

A 55-year-old man was hospitalized for a low back pain lasting for 3 months. Spinal MRI revealed a suggestive aspect of multilevel discitis L5-S1-S2 with paravertebral abscess. A thoraco-abdominal CT scan confirmed the presence of multiple pathological lymph nodes in several locations, bilateral micronodular pulmonary infiltrate; it also showed mirror bone erosions of vertebral L5 and S1 endplates, suggestive of disseminated tuberculosis with lung involvement and lymphadenopathy. A discovertebral L5-S1 biopsy was performed confirming the diagnosis of metastatic prostatic adenocarcinoma including a tumor infiltration of the intervertebral disc, without arguments for a septic processus superimposed without tuberculosis granuloma. Although rare, cases of metastases located at the disco-vertebral junction including prostatic cancer have already been described, and should be known to the clinician. The differential diagnosis with an infectious spondylodiscitis can be difficult in some case around the vertebral disc and in case of epiduritis and soft tissues involvement on MRI sequences. Disco-vertebral biopsy remains the cornerstone of the diagnosis.

GOSPEL 3: Management of gout by primary-care physicians and office-based rheumatologists in France in the early 21st century - comparison with 2006 EULAR Recommendations.

INTRODUCTION: In 2006, recommendations about the management of gout were issued by the European League Against Rheumatism (EULAR). The objective of this work was to compare these recommendations to practice patterns of physicians working in private practices in France. METHOD: In a prospective multicenter nationwide study conducted in France, a random sample of primary-care physicians (PCPs) and private-practice rheumatologists (PPRs) was taken in 2009. Each physician included 2 consecutive patients with gout. Each patient was evaluated twice at an interval of 3-6months. Information on EULAR 2006 management modalities were collected in a standardized manner. RESULTS: Of 1003 patients, 771 were evaluated twice. Allopurinol was prescribed to 75.1% of patients in all and was initiated at the first study visit in 44 patients, among whom 19 (43.2%) 19 patients received the recommended starting dosage of 100mg/day. Colchicine therapy to prevent flares was prescribed to 74.3% of patients. Of the 522 patients on allopurinol therapy at the first visit, only 34.5% had serum uric acid levels≤360µmoL/L (mean dosage, 173 mg/day). Excessive dietary intake by patients who were overweight or obese was recorded in 31.5% of patients seen by PCPs and in 19.7% of those seen by OBRs. This finding prompted the delivery of nutritional advice to 45.8% of patients. Discontinuation of excessive alcohol intake was recommended to only 10% of patients. Diuretic therapy discontinuation was feasible in 175 patients but was recommended in only 7 patients. CONCLUSION: Differences between practice patterns and 2006 EULAR recommendations were identified. Simplifying the recommendations and teaching them during medical training and continued medical education may deserve consideration.

First case of osteopathia striata with cranial sclerosis in an adult male with Klinefelter syndrome.

Osteopathia striata with cranial sclerosis is a rare X-linked disorder. It is often lethal in male patients, and is considered X-linked dominant since affected females exhibit clinical signs, although milder than males. We describe here an adult male patient, with clinical and radiological signs similar to those described in female patients. Diagnosis was confirmed by the identification of an AMER1 mutation. The presence of long bones striation and the clinical phenotype of the patient also led to the diagnosis of non-mosaic Klinefelter syndrome, probably explaining the non-lethal and even rather minor phenotype compared to the rare affected males already described.

Risk factors of mortality during the first year after low energy osteoporosis fracture: a retrospective case-control study.

INTRODUCTION: Osteoporotic fractures are a major public health problem because of the morbidity and mortality of fracture complications. The objective of this study was to examine predictive factors of mortality during the first year after an osteoporotic fracture. METHODS: It is a retrospective case-control study using data of a group of 1081 patients aged over 50 years with severe osteoporotic fractures by the Rennes university hospital emergency department from August 2007 to September 2008. Patients (cases) who died during the year following the fracture were compared with others who had survived (controls) one year after the fracture, matched on age, sex and type of fracture. Pre-fracture comorbidities and complications after the fractures were studied. RESULTS: Forty-two cases and 126 controls were analyzed without significant differences in age, sex or type of fracture. On univariate analysis, previous neoplasia, neurodegenerative disease, walking aids, thromboembolic complication, post fracture infection, post fracture heart failure, post fracture acute respiratory failure were associated with more mortality after osteoporotic fracture. After multivariate analysis, only previous neoplasia (OR = 4.63 [1.79 - 11.95]; p = 0.02) and acute respiratory failure after fracture (OR = 28.15 [5.75 - 137.9]; p<0.001) were retained as predictive factors during the year following the fracture. CONCLUSION: Patients died more often from their co-morbidities than direct complications of their fractures. Osteoporotic fracture seems to be a marker of poor health status and a factor which may hasten the death.

French law: what about a reasoned reimbursement of serum vitamin D assays?

The number of serum 25-hydroxyvitamin D (25OHD) assays has increased tenfold in France in less than 10 years, sometimes for invalidated reasons. In 2013, the French National Authority for Health (Haute autorité de santé, or HAS) limited the indications for serum 25OHD measurements to rickets/osteomalacia, older adults with recurrent falls, monitoring of kidney transplant in adults, and surgical treatment of obesity in adults. Our aim here was to note that other indications for serum 25OHD measurements are supported by previous literature and by a number of national and international recommendations, in particular the following: any situation of bone fragility, any chronic renal failure <45 mL/min/1.73m2, any situation of malabsorption, clinical signs consistent with vitamin D deficiency or vitamin D overload, and calcium phosphorus evaluation. We suggest that the measurement of serum 25OHD concentration should remain reimbursed as part of these extended indications.

Mid-infrared fibre evanescent wave spectroscopy of serum allows fingerprinting of the hepatic metabolic status in mice.

Non-alcoholic fatty liver disease is associated with obesity, diabetes, and metabolic syndrome. The detection of systemic metabolic changes associated with alterations in the liver status during non-alcoholic fatty liver disease could improve patient follow-up. The aim of the present study was to evaluate the potential of mid-infrared fibre evanescent wave spectroscopy as a minimum-invasive method for evaluating the liver status during non-alcoholic fatty liver disease. Seventy-five mice were subjected to a control, high-fat or high-fat-high carbohydrate diets. We analysed the serum biochemical parameters and mRNA levels of hepatic genes by quantitative RT-PCR. Steatosis was quantified by image analysis. The mid-infrared spectra were acquired from serum, and then analysed to develop a predictive model of the steatosis level. Animals subjected to enriched diets were obese. Hepatic steatosis was found in all animals. The relationship between the spectroscopy-predicted and observed levels of steatosis, expressed as percentages of the liver biopsy area, was not linear. A transition around 10% steatosis was observed, leading us to consider two distinct predictive models (<10% and >10%) based on two different sets of discriminative spectral variables. The model performance was evaluated using random cross-validation (10%). The hypothesis that additional metabolic changes occur beyond this transition was supported by the fact that it was associated with increased serum ALT levels, and Col1α1 chain mRNA levels. Our data suggest that mid-infrared spectroscopy combined with statistical analysis allows identifying serum mid-infrared signatures that reflect the liver status during non-alcoholic fatty liver disease.