Bone lesions in systemic mastocytosis: Bone histomorphometry and histopathological mechanisms.

Osteoporosis is considered the most frequent skeletal manifestation of systemic mastocytosis (SM). We performed a retrospective analysis of sixty patients (37 males and 23 females) who underwent a bone biopsy in the assessment of SM or in the assessment of unexplained bone fragility. Thirty-three had simultaneously a bone marrow biopsy with a Jamshidi's needle; this sample was used for immunohistochemical analysis (tryptase, c-KIT. CD20, VCAM-1). Bone biopsy was realized in 42 cases in the assessment of SM to provide histologic proof of the disease and in 18 cases in the assessment of unexplained bone fragility and surprisingly revealed a SM. An increased bone turnover was observed in patients with SM with elevated eroded surfaces, osteoclast number and bone formation rate. In addition to nodules of mast cells (MC), a high number of MC was directly apposed on the trabeculae, affixed on the osteoblasts or the lining cells. The VCAM-1 adhesion protein recognizing α4ß7 and α4ß1 integrins may be a candidate to explain this particular adherence. One third of the bone marrow biopsies did not exhibit MC nodules or MC infiltration and led to a false negative diagnosis for SM. SM can be discovered in the assessment of fracture or osteoporosis. Transiliac bone biopsy allows for the diagnosis of the disease more accurately than bone marrow biopsy; it also provides a histomorphometric analysis of bone remodeling.

Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect.

BACKGROUND: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. OBJECTIVES: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. METHODS: This was an independently conducted post hoc analysis of the moderate-to-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg-1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg-1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24-month efficacy and safety results were also reported. RESULTS: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. CONCLUSIONS: In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus. Corticosteroids, a standard first-line treatment for PV, have significant side-effects. Although their effects are unproven, adjuvant corticosteroid-sparing agents are routinely used to minimize steroid exposure and corticosteroid-related side-effects. There is evidence that the anti-CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator-initiated trial. Rituximab plus prednisone had a steroid-sparing effect and more patients achieved complete remission off prednisone. Fewer patients experienced grade 3 or grade 4 steroid-related adverse events than those on prednisone alone. This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate-to-severe PV.

Volumetric Absorptive Microsampling (VAMS) technology for IGF-1 quantification by automated chemiluminescent immunoassay in dried blood.

For medical diagnostics and anti-doping analyses, insulin-like growth factor 1 (IGF-1) can be measured in serum using automated chemiluminescent immunoassays. The aim of this study was to assess the feasibility of using dried blood instead of serum to measure IGF-1 concentrations with an automated IGF-1 immunoassay and to evaluate if IGF-1 concentrations from dried capillary blood and serum were comparable. Blood samples (venous blood and capillary blood obtained from the arm skin using a device from Seventh Sense Biosystem) were collected with 20 µL Volumetric Absorptive Micro samplers (VAMS) (Mitra®, Neoteryx). These samplers offer the possibility of collecting a fixed volume of blood without perturbation by hematocrit. Starting from dried blood, an aqueous desorption in 0.9% NaCl was efficient to release IGF-1. The solution was directly analyzed on the automated IGF-1 immunoassay. IGF-1 concentrations after extraction from VAMS were lower than in serum (due to the dilution performed for the elution of IGF-1) but measurable for serum concentrations over 50 ng/mL. In addition, IGF-1 on VAMS was stable for at least one month at room temperature. Following adjustment for dilution, serum and dried blood IGF-1 concentrations were of the same order. However lower concentrations were obtained from the capillary blood in particular for high serum concentrations. In conclusion, a micro volume of dried capillary blood could be used to quantify IGF-1 with an automated chemiluminescent immunoassay. However, more data are needed to establish specific IGF-1 reference concentrations using dried capillary blood instead of serum.

Methotrexate efficacy and tolerance in plaque psoriasis. A prospective real-life multicentre study in France.

BACKGROUND: Methotrexate (MTX) is a major systemic treatment for moderate to severe plaque psoriasis. A randomized trial has recently been published evaluating a single weekly dosage (17.5mg), but few prospective real-life data are available. The main objective of this study was to prospectively evaluate the efficacy of MTX in real-life. The secondary objectives were to evaluate predictive parameters for treatment efficacy and the frequency of adverse events. PATIENTS AND METHODS: A prospective cohort involving consecutive at in 25 centres belonging to GEM RESOPSO included all adults with plaque psoriasis in whom MTX treatment was initiated. The efficacy criterion was achievement of PASI 75 at week (W) 12/16. The impact of demographic data, psoriasis characteristics (duration, topography, rheumatism), dosage (W12/16 dosage, cumulative dose after 4 weeks), and mode of administration (subcutaneous vs. oral, concomitant use of folic acid) on efficacy was evaluated. Intention-to-treat (ITT),per protocol (PP), and multivariate analyses were performed. RESULTS: Two hundred and fifty-six patients (F/M: 105/151; mean age: 45.0 years; rheumatism: 12.6%) with plaque psoriasis were included. 99 patients were not analysed at W12/16 (16 because of inefficacy, 16 because of intolerance, 56 were lost to follow-up or had data missing). PASI 75 was achieved in 98 patients, with efficacy of 38.3% in the ITT analysis and 58.3% in the PP analysis. In the ITT analysis, absence of previous use of cyclosporine (P=0.01) and a cumulative dose of MTX>60mg after 4 weeks (P<0.0001) were associated with higher PASI 75 rates. In the PP analysis, only absence of previous use of cyclosporine (P=0.0009) was associated with a better PASI 75 results. There was no association between PASI 75 and patient characteristics (including body mass index), clinical aspects of psoriasis, route of administration, combination with folic acid, or W12/16 dose. Adverse events were reported by 34.8% of patients. These consisted mainly of digestive disorders (nausea, abdominal pain), asthenia and moderate hepatic cytolysis. The frequency of adverse events was correlated with methotrexate dosage. DISCUSSION: The efficacy of MTX in plaque psoriasis in this real-life study of 256 patients is consistent with the data in the literature, including the recently published randomized trial (41% PASI 75). This rate was unaffected by patient weight, route of administration and combined use of folic acid. Absence of previous use of cyclosporine appears to be associated with better efficacy although there is no clear explanation for this. The initial dosage (high dose in the first month) appears to be associated with superior efficacy for W12/W16.

Neuroendocrine and inflammatory responses to DHEA administration in young healthy women.

DHEA is reported to have beneficial effects for the elderly and for several pathologies because of its behavioral and anti-inflammatory properties. However, these properties have never been investigated in a young healthy population. The purpose of this double-blind, randomized study was therefore to investigate the effects of short-term DHEA administration (100 mg/day/4 weeks) on neuroendocrine (i.e., beta-endorphin and prolactin) and inflammatory (i.e., interleukin-6 and TNF-alpha) parameters in 10 young healthy female volunteers with regular sports practice. In parallel, the stress state was assessed with the Profile of Mood States (POMS) questionnaire. DHEA administration did not alter prolactin, interleukin-6 or TNF-alpha, and no significant change in tension, depression, anger, vigor, fatigue or confusion was noted. However, beta-endorphin levels increased significantly (p < 0.05) with the DHEA treatment. The results of this investigation indicate that short-term DHEA administration improves neuroendocrine modulation but does not affect the inflammatory status or psychological state in recreationally trained female athletes. Further studies are needed to determine the exact mechanisms and the responses of these parameters to DHEA administration at higher dosages and/or for longer durations, especially in response to physical/psychological stress.

A validated, sensitive electrophoretic method for the detection of activin receptor type II-Fc fusion proteins in human blood.

New therapeutic proteins that trap circulating members of the transforming growth factor (TGF) beta superfamily (activins and growth differentiation factors) show promising effects on erythropoiesis and muscular growth. They are dimeric recombinant fusion proteins composed of the extracellular domain of a human activin receptor (ActRIIA or IIB) linked to the Fc part of human IgG1. Sotatercept (ActRIIA-Fc) and Luspatercept (a modified ActRIIB-Fc) in particular are now in phase 2/3 of clinical trials against anemia and included in the prohibited list established by the World Anti-Doping Agency. To prevent a potential misuse by athletes in the near future, a robust and sensitive method of detection is needed. We validated an approach adapted from an electrophoretic method used for the detection of recombinant erythropoietins that allowed detection of various ActRIIA-Fc and ActRIIB-Fc proteins, including variants produced in different cell types, after a single immuno-extraction step. After separation by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), an initial testing procedure performed by single-blotting can indicate the presence of an ActRII-Fc (indifferently type IIA or IIB). A confirmation performed by double-blotting using different antibodies for detection allows a more precise identification of the type of ActRII-Fc (IIA, IIB). Starting from a few hundred microliters of serum or plasma, this method is specific, sensitive, and easy to perform. It could easily be adopted by anti-doping laboratories.

Implementation of AICAR analysis by GC-C-IRMS for anti-doping purposes.

AICAR (5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside), is a naturally occurring substance which is part to the World Anti-Doping Agency (WADA) Prohibited List. It is claimed to improve physical performance when administered as a supplement. As for other endogenous compounds such as steroids, the gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) analysis remains an efficient tool to differentiate endogenous substances from exogenous ones. A protocol was described in the literature for the analysis of AICAR by GC-C-IRMS. The aim of the present study was to implement this protocol in our laboratory and to propose solutions to avoid the difficulties encountered. The first point discussed in this study is the derivatization step. Due to the structure of the AICAR molecule, conventional derivatization for GC-C-IRMS such as acetylation could not be applied and silylation was preferred. The improvement of the derivatives stability was achieved thanks to several derivatization conditions tested. This adjustment led to a reproducible derivatization pattern with the 3-TMS form as major derivative product. The second point discussed in this study is the diminution of extracts' background noise. Indeed, the implementation of the published protocol was not easy due to high performance liquid chromatography (HPLC) problems encountered when concentrated urine was injected into our system. Also, too many interferences in the endogenous reference compound fractions were observed. The addition of both a wash step before the HPLC purification and a HPLC purification step for the endogenous reference compound (ERC) fraction allowed us to increase the robustness of the method. This study presents the modified protocol compared to the original protocol as well as the evaluation of the whole method performances. Copyright © 2017 John Wiley & Sons, Ltd.

Chronic alcohol abuse in men alters bone mechanical properties by affecting both tissue mechanical properties and microarchitectural parameters.

OBJECTIVE OF THE STUDY: Alcohol-induced secondary osteoporosis in men has been characterized by higher fracture prevalence and a modification of bone microarchitecture. Chronic alcohol consumption impairs bone cell activity and results in an increased fragility. A few studies highlighted effects of heavy alcohol consumption on some microarchitectural parameters of trabecular bone. But to date and to our knowledge, micro- and macro-mechanical properties of bone of alcoholic subjects have not been investigated. PATIENTS: In the present study, mechanical properties and microarchitecture of trabecular bone samples from the iliac crest of alcoholic male patients (n=15) were analyzed and compared to a control group (n=8). MATERIALS AND METHODS: Nanoindentation tests were performed to determine the tissue's micromechanical properties, micro-computed tomography was used to measure microarchitectural parameters, and numerical simulations provided the apparent mechanical properties of the samples. RESULTS: Compared to controls, bone tissue from alcoholic patients exhibited an increase of micromechanical properties at tissue scale, a significant decrease of apparent mechanical properties at sample scale, and significant changes in several microarchitectural parameters. In particular, a crucial role of structure model index (SMI) on mechanical properties was identified. CONCLUSIONS: 3D microarchitectural parameters are at least as important as bone volume fraction to predict bone fracture risk in the case of alcoholic patients.

Osteoporosis in Stickler syndrome. A new family case with bone histology study.

The Stickler syndrome (SS) has been described as a "hereditary progressive arthro-ophtalmopathy" by Stickler in 1965, due to mutations on the collagen genes. Currently about 40 different genes have been identified which encode for at least 27 different collagens. The majority of mutations occur in the COL2A1 gene on chromosome 12q13 (SS type I). Mutations in COL11A1 are less frequent (SS type II). More recently, mutations in COL11A2 and in the COL9A1 gene have been reported with particular phenotypes. The main features of this autosomal inherited disease are ocular, auditory with orofacial abnormalities and early-onset osteoarthritis. We report the clinical presentation of an adult and his son, with a particular focus on the bone status of the father, radiography, bone densitometry and transiliac bone biopsy showing that he was suffering from osteoporosis. The lumbar bone mineral density was low with a Z-score at -2.9. Transiliac bone biopsy showed a dramatic decrease of trabecular bone volume (8.6%; Nl: 19.5±4.9%), thin trabeculae and a disorganized trabecular network. A slight increase of osteoid parameters was observed. Bone resorption was markedly increased with an excessive number of active (TRAcP+) osteoclasts. The cortical width was normal, but a slight increase of cortical porosity was found. Osteoporosis has been rarely described in the SS. It might be useful to systematically perform a bone densitometry in all patients with SS and to discuss the indication of a transiliac bone biopsy in severe cases.

New-onset vitiligo and progression of pre-existing vitiligo during treatment with biological agents in chronic inflammatory diseases.

BACKGROUND: The development of vitiligo during treatment with biological agents is an unusual event and only a few isolated cases have been reported. OBJECTIVES: To describe the clinical characteristics and evolution of patients developing new-onset vitiligo following initiation of a biological agent for chronic inflammatory disease; and also to report the clinical course of pre-existing vitiligo under biological therapy. METHODS: This nationwide multicentre, retrospective study, carried out between July 2013 and January 2015, describes the characteristics of a large series of 18 patients (psoriasis N = 8, inflammatory rheumatic diseases N = 8, ulcerative colitis N = 1, uveitis N = 1) who developed new-onset vitiligo while receiving a biological agent. RESULTS: TNFα inhibitors were the most common biological agent involved (13/18) while anti-IL-12/23 and anti-IL-17 agents or abatacept were less common (4/18 and 1/18 respectively). Mean duration of biological agent exposure before vitiligo onset was 13.9 ± 16.5 months. Outcome was favourable for most patients (15/17) while maintaining the biological agent. Data were also collected for 18 patients (psoriasis N = 5, inflammatory rheumatic diseases N = 10, inflammatory bowel diseases N = 2, SAPHO N = 1) who had pre-existing vitiligo when treatment with a biological agent started (TNFα inhibitors N = 15, ustekinumab N = 1, rituximab N = 1, tocilizumab N = 1). Vitiligo progressed in seven patients and was stable or improved in eight cases. CONCLUSION: Vitiligo may thus emerge and/or progress during treatment with various biological agents, mainly TNFα inhibitors and could be a new paradoxical skin reaction. De novo vitiligo displays a favourable outcome when maintaining the biological agent, whereas the prognosis seems worse in cases of pre-existing vitiligo.

[Recommendations for patients on preparing for dermatology-allergology consultations: Evaluation of the information notice of the French Society for Dermatology]. / Recommandations au patient avant les tests cutanés : évaluation de la fiche d'information du groupe dermato-allergologie de la Société française de dermatologie.

BACKGROUND: Skin patch-tests in dermatology-allergology practice require good preparation. To this end, the dermatology-allergology group of the French Society of Dermatology introduced an information notice informing patients about patch testing procedures. The aim of this study was to evaluate the utility and understanding of the notice. PATIENTS AND METHODS: The information notice was sent out to patients before testing. On the day of the test, a questionnaire was submitted to patients to evaluate their comprehension of the notice. Another questionnaire was submitted simultaneously to the dermatology-allergology practitioner to evaluate whether the patient had complied with the guidelines given in the information notice. Paired questionnaires were analyzed for this study. RESULTS: Eight dermatology-allergology hospital departments participated in the study and collected 921 paired questionnaires over a period of 18months. Among the vast majority (96.2%) of patients who had read the information notice, most found it useful (98.8%), easy to read (97.4%), and appropriate (91.5%). Ten percent of patients had difficulty understanding. CONCLUSION: This study shows that the information notice was clear and explicit for the immense majority of patients. Thanks to the feedback of a number of patients, the information notice was further improved to enhance patient understanding.

Fibrodysplasia ossificans progressiva. A case report and focus on the BMP signaling pathway.

Fibrodysplasia ossificans progressiva is a very rare heritable disease characterized by a progressive heterotopic endochondal ossification, occurring in the first decade of life, and leading thereafter to a severe ankylosis of the spine, limbs and jaw, with a progressive and severe functional disability. To date the cause of the disease remains unknown and no medical treatment has been proved efficient. It has recently been shown that a recurrent mutation in activation domain of the activin-receptor IA (ACVR1), a BMP receptor, could lead to an abnormal signalling pathway of BMP-4 and contribute to the occurrence of the devastating lesions characteristic of the disease.

Prognostic value of antibodies to Merkel cell polyomavirus T antigens and VP1 protein in patients with Merkel cell carcinoma.

BACKGROUND: Merkel cell polyomavirus (MCPyV) is the main aetiological agent of Merkel cell carcinoma (MCC). Serum antibodies against the major MCPyV capsid protein (VP1) are detected in the general population, whereas antibodies against MCPyV oncoproteins (T antigens) have been reported specifically in patients with MCC. OBJECTIVES: The primary aim was to assess whether detection of serum antibodies against MCPyV proteins at baseline was associated with disease outcome in patients with MCC. The secondary aim was to establish whether evolution of these antibodies during follow-up was associated with the course of the disease. METHODS: Serum T-antigen and VP1 antibodies were assessed by enzyme-linked immunosorbent assay using recombinant proteins in a cohort of 143 patients with MCC, including 84 patients with serum samples available at baseline. RESULTS: Low titres of VP1 antibodies at baseline (< 10 000) were significantly and independently associated with increased risk of recurrence [hazard ratio (HR) 2·71, 95% confidence interval (CI) 1·13-6·53, P = 0·026] and death (HR 3·74, 95% CI 1·53-9·18, P = 0·004), whereas T-antigen antibodies were not found to be associated with outcome. VP1 antibodies did not differ between patients in remission and those with recurrence or progression during follow-up. However, T-antigen antibodies were more frequently detected in patients with recurrence or progression at 12 months (P = 0·020) and 24 months (P = 0·016) after diagnosis. CONCLUSIONS: VP1 antibodies constitute a prognostic marker at baseline, whereas T-antigen antibodies constitute a marker of disease recurrence or progression if detected > 12 months after diagnosis.

Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance.

Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with κ light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80-11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density.

Comparison between quantitative X-ray imaging, dual energy X-ray absorptiometry and microCT in the assessment of bone mineral density in disuse-induced bone loss.

OBJECTIVES: We recently introduced a new methodology called quantitative X-ray imaging (qXRI) to investigate bone mineral density in isolated rodent bones. The aims of the present study were to compare DXA and microCT with qXRI in a rat model of disuse osteoporosis. METHODS: Fourteen Copenhagen rats were injected with a single dose of botulinum toxin (BTX - 2 UI) in the right Mus quadriceps femoris. The left hindlimb serves as control. Areal BMD and vBMD were determined with a Hologic Discovery-W device and a Skyscan 1172 microcomputed tomograph (microCT). Absorbing material density (AMD) was determined on digitized X-ray images obtained with a Faxitron M020 device. RESULTS: All three methods highlighted significant lower values for aBMD, vBMD and AMD in trabecular and cortical bone in the BTX-injected side. In trabecular bone, aBMD, vBMD and AMD were significantly correlated with BV/TV. In cortical bone, only aBMD and vBMD were significantly correlated with cortical bone mass On the other hand, only AMD was significantly correlated with the mechanical parameters bending strength and bending modulus. CONCLUSIONS: qXRI is a rapid and cheap method to assess trabecular bone mass in isolated rodent bones and can be used as a surrogate for the densitometry of small animals.

[Therapeutic patient education in chronic hand dermatitis]. / Éducation thérapeutique du patient dans l'eczéma chronique des mains.

Hand dermatitis (HD) is usually due to a combination of various interacting factors. It involves significant impairment of the quality of life with psychological and socioeconomic impact. A therapeutic education program in HD.was elaborated by 19 health professionals (dermatologists, occupational clinical physicians, nurses, psychologists, environmental medical advisor) with experience in therapeutic education or skills in HD, according to the recommendations of Haute Autorité de Santé. The program includes an individual medical consultation to perform educational diagnostic, two collective workshops and a medical evaluation consult. Two group workshops "the disease, irritant factors and its treatments" and "the experiences and feelings" were elaborated with learning objectives and educative tools. Different scores were proposed to evaluate the program and acquired skills. Therapeutic education is an efficient way to help patients to adopt skin protection measures essential to healing. We propose a guideline of therapeutic education in HD including skills and educative tools and intended for health professionals to serve as working basis.

Fracture incidence after 3 years of aromatase inhibitor therapy.

BACKGROUND: The purpose of this study was to describe the fracture incidence and bone mineral density (BMD) evolution in a large cohort of post-menopausal women with breast cancer after 3 years of aromatase inhibitor (AI) therapy. PATIENTS AND METHODS: A prospective, longitudinal study in real-life setting. Each woman had an extensive medical assessment, a biological evaluation, a BMD measurement, and systematic spinal X-rays at baseline and after 3 years of AI therapy. Women with osteoporosis at baseline (T-score < -2.5 and/or non-traumatic fracture history) were treated by oral weekly bisphosphonates. RESULTS: Among 497 women (mean age 63.8 ± 9.6 years) included in this study, 389 had a bone evaluation both at baseline and after 3 years of AI therapy: 267 women (mean age 61.2 ± 8.6) with no osteoporosis at baseline and 122 women (mean age 67.2 ± 9.1) with osteoporosis at baseline justifying a weekly oral bisphosphonate treatment. Women without bisphosphonates had a significant decrease in spine BMD (-3.5%, P < 0.01), neck BMD (-2.0%, P < 0.01), and total hip BMD (-2.1%, P < 0.01) over the 3 years but only 15 of them (5.6%) presented an incident vertebral or non-vertebral fracture. In osteoporotic women treated with bisphosphonates, spine and hip BMD were maintained at 3 years but 12 of them (9.8%) had an incident fracture. These fractured women were significantly older (74.1 ± 9.8 versus 66.5 ± 8.8) but also presented BMD loss during treatment suggesting poor adherence to bisphosphonate treatment. CONCLUSION: This real-life study confirmed that AIs induced moderate bone loss and low fracture incidence in post-menopausal women without initial osteoporosis. In women with baseline osteoporosis and AI therapy, oral bisphosphonates maintain BMD but were associated with a persistent fracture risk, particularly in older women.

Vitamin D deficiency is associated with greater tumor size and poorer outcome in Merkel cell carcinoma patients.

BACKGROUND: Merkel cell polyomavirus has been recognized to be associated with Merkel cell carcinoma (MCC), but the evolution of this cancer probably depends on various factors. Vitamin D deficiency, defined by serum 25-hydroxyvitamin D levels <50 nmol/L, seems to influence cancer behavior and progression, but has never been assessed in MCC patients. OBJECTIVES: First, to evaluate whether vitamin D deficiency was associated with tumor characteristics and prognosis in a cohort of MCC patients. Second, to assess expression of the vitamin D receptor (VDR) in MCC tumors. METHODS: Clinical findings, Merkel cell polyomavirus markers and vitamin D status were assessed in a cohort of French MCC patients. The study was limited to the 89 patients for whom the serum sample had been collected within 3 years after the diagnosis of MCC. Correlation between vitamin D deficiency and MCC characteristics and outcome were determined in regression analyses. VDR expression in MCC tumours was assessed by immunohistochemistry. RESULTS: Vitamin D deficiency was noted in 65.1% of the patients and was independently associated with greater tumor size at diagnosis (P = 0.006) and with metastasis recurrence (HR, 2.89; 95% CI, 1.03 to 8.13; P = 0.043), but not with death from MCC, although there was a trend (HR, 5.28; 95% CI, 0.75 to 36.96; P = 0.093). VDR was found to be strongly expressed in all 28 MCC tumor specimens investigated. CONCLUSION: The association between vitamin D deficiency and MCC characteristics and outcome, together with detection of the VDR in MCC cells, suggest that vitamin D could influence the biology of MCC.