Percutaneous Fixation with Internal Cemented Screws for Iliac Lytic Bone Metastases: Assessment of Pain and Quality of Life on Long Term Follow-up.

PURPOSE: To assess effectiveness on pain, quality of life and late adverse events of percutaneous fixation with internal cemented screw (FICS) among patients with iliac lytic bone metastases with or without pathological fractures. MATERIALS AND METHODS: This retrospective exploratory study analyzed FICS procedures on iliac osteolytic bone lesions with and without pathological fracture performed from July 2019 to January 2022 in one tertiary level university hospital. The procedure were performed under general anesthesia, and were CT and fluoroscopically guided. Numerical Pain Rate Score (NPRS), mean EuroQol visual analogue scale (EQ VAS), morphine consumption, walking ability, walking perimeter and presence of walking aids and the appearance of complications were evaluated. RESULTS: Nineteen procedures among 18 patients were carried out with a mean follow up time of 243.3 ± 243.2 days. The mean of the maximum NPRS decreased from 8.4 ± 1.3 to 2.2 ± 3.1 at 1 month (p < 0.01) and remained between 1.3 and 4.1 during a follow-up consultation period of 3-24 months. The mean EQ VAS rose from 42.0 ± 12.5 to 57.3 ± 13.9 at 1 month (p < 0.01) follow-up and remained between 55.8 and 62.5 thereafter. No patient scores returned to pre-procedure levels during follow-up. Mean morphine use decreased from 111.1 ± 118.1 to 57.8 ± 70.3 mg/d at 1 month (p > 0.05) follow-up. No late adverse events were reported. CONCLUSION: Percutaneous FICS is a safe procedure with fast and long-standing effect on pain, mobility and quality of life. It can be used as a complement to the known analgesic therapeutic arsenal for bone metastases.

Narrative Review of Effects of Glucagon-Like Peptide-1 Receptor Agonists on Bone Health in People Living with Obesity.

Glucagon-like peptide-1 Receptor agonists (GLP-1Ras) such as liraglutide and semaglutide have been recently approved as medications for chronic weight management in people living with obesity (PwO); GLP-1 may enhance bone metabolism and improve bone quality. However, the effects of GLP-1Ras on skeletal health remain to be determined and that's the purpose of this narrative review. Nevertheless, bone consequences of intentional weight loss interventions in PwO are well known: (i) significant weight loss induced by caloric restriction and bariatric surgery results in accelerated bone turnover and bone loss, and (ii) unlike caloric restriction interventions, PwO experience a substantial deterioration in bone microarchitecture and strength associated with an increased risk of fracture after bariatric surgery especially malabsorptive procedures. Liraglutide seems to have a positive effect on bone material properties despite significant weight loss in several rodent models. However, most of positive effects on bone mineral density and microarchitecture were observed at concentration much higher than approved for obesity care in humans. No data have been reported in preclinical models with semaglutide. The current evidence of the effects of GLP-1Ra on bone health in PwO is limited. Indeed, studies on the use of GLP-1Ra mostly included patients with diabetes who were administered a dose used in this condition, did not have adequate bone parameters as primary endpoints, and had short follow-up periods. Further studies are needed to investigate the bone impact of GLP-1Ra, dual- and triple-receptor agonists for GLP-1, glucose-dependent insulin releasing polypeptide (GIP), and glucagon in PwO.

Advanced practice nurse management in multiple myeloma treated with oral therapy.

INTRODUCTION: Therapeutic approaches in Multiple Myeloma (MM) have considerably changed over the last few years, with effective oral chemotherapy and continuous treatment. In this context, the objective of this study was to examine the circuitry of an advanced practitioner nurse (APN)-led intervention that provided supportive care for MM patients treated with oral chemotherapy. METHODS: This population-based study was conducted at the hematology department - Institut de Cancérologie Lucien Neuwirth (ICLN, Saint-Priest-en-Jarez), from April 2017 to September 2020. A follow-up program was established with a specialized APN in oncology. RESULTS: All APN interventions were recorded, representing 1240 phone calls and 162 consultations for 42 MM patients. Eighty-two calls were referred to the physician with 45 consultations triggered. Most of the calls were frequent within the few first months, with a high request for information and reassurance, especially for treatment-naive or relapsed patients. In our study, the APN was able to manage multiple side effects through care organization (i.e., hospitalizations, transfusions) and a careful coordination between the primary care team and the hospital. DISCUSSION: In order to respond to the high need for care pathway and safety improvement, especially in elderly population, we have initiated an original follow-up by an APN for MM patients treated with oral chemotherapy. While the role of APN has become prominent in the oncology field in recent years, its holistic approach has to be emphasized in further studies to bring a comprehensive perspective to health care coordination in the future.

Factors associated with COVID-19 severity in patients with spondyloarthritis: Results of the French RMD COVID-19 cohort.

OBJECTIVES: The objective of the current study was to evaluate the severity of COVID-19 and identify factors associated with severe disease outcomes in patients with spondyloarthritis (SpA), a chronic inflammatory rheumatic and musculoskeletal disease (RMD). METHODS: We utilized patient data from the French national multicenter RMD COVID-19 cohort (NCT04353609). The primary outcome was to describe COVID-19 characteristics in patients with SpA based on disease severity of COVID-19 (mild, moderate or severe) with serious infection including moderate and severe cases. The secondary outcome was to identify the factors associated with serious COVID-19 classification. RESULTS: Among the 626 patients with SpA (56% female, mean age 49±14 years) from the French RMD cohort, COVID-19 severity was mild in 508 (81%), moderate in 93 (15%), and severe in 25 (4%) patients. Clinical signs and symptoms of COVID-19 were reported in 587 (94%) patients, with the most frequent presented symptom of fever (63%) and cough (62%), followed by flu-like symptoms (53%), agueusia (39%), anosmia (37%), dyspnea (32%) and diarrhea (19.9%). COVID-19 severity was associated with corticosteroid therapy (OR=3.08 [95% CI: 1.44-6.58], P=0.004) and age (OR=1.06 [95% CI: 1.04-1.08], P<0.001) while use of tumor necrosis factor inhibitor (TNFi, OR=0.27 [95% CI: 0.09-0.78], P=0.01) was associated with less severe disease. We did not identify an association between NSAID use and COVID-19 severity. CONCLUSIONS: In this study, the majority of patients with SpA had a favorable COVID-19 outcome. We confirmed age and corticosteroids therapy had a negative impact on disease outcomes while TNFi use was protective.

Combination of Percutaneous Screw Fixation and Cementoplasty for Lytic Bone Metastases: Feasibility, Safety and Clinical Outcomes.

OBJECTIVE: To evaluate feasibility, safety and efficacy of a combination of screw fixation and cementoplasty for pathologic bone fracture. METHODS: In this single-center prospective study, all consecutive percutaneous screw fixations under assisted CT guidance for palliation and fracture treatment of pathologic bone fracture were reviewed from July 2019 to February 2021. The primary outcome measure was the procedures' technical success, defined as the correct placement of the screw(s), without any complications. Secondary outcome measures were the safety, the procedures' early analgesic effects and impacts on quality of life at 4 weeks. RESULTS: Technical success was achieved in 11/11 procedures (100%) among 11 patients. No major complications attributable to the procedure were noted. The mean pain scored significantly decreased at the initial follow-up: 8.0 ± 2.7 versus 1.6 ± 2.5 (p < 0.05). Opioid doses were statistically lower after procedure: 70.9 ± 37 versus 48.2 ± 46 mg/day (p < 0.05). The mean EQ5D score had significantly increased by the early post-procedure consultation: 42.5 ± 13.6 vs 63.6 ± 10.3 (p < 0.05). CONCLUSION: Combination of percutaneous screw fixation and cementoplasty for pathologic bone fracture is feasible and safe. It is efficient to reduce pain, decrease the consumption of opioids and improve the quality of life at 4 weeks after the procedure.

Management of bone fragility in patients with rheumatoid arthritis in France: An analysis of a national health insurance claims database.

OBJECTIVES: Rheumatoid arthritis (RA) is considered a major risk factor for fragility fractures. We examined the quality of management of bone fragility in RA patients in a real-life setting. METHODS: We performed a longitudinal case-control retrospective study in a 1/97th random sample of French health care claims database from 2014 to 2016 to determine the extent of bone fragility management in patients with RA compared with non-RA matched controls. RESULTS: Compared to their non-RA controls (n=4652), RA patients (n=1008; mean age: 61.1years; methotrexate: 69.7%; other conventional disease-modifying antirheumatic drugs (cDMARDs): 26.8%; biologic: 26.0%; corticosteroids: 36.9%) had more reimbursements for bone mineral density (BMD) measurements (21.6 vs. 9.2%; OR=2.7 [2.3; 3.3]; P<0.01) and for bisphosphonates (7.1 vs. 3.6%, OR=2.0 [1.5; 2.7]; P<0.05). In patients exposed to corticosteroids, RA patients underwent more BMD assessments than non-RA controls (28.0 vs. 18.8%; OR=1.7 [1.3; 2.2]; P<0.05). RA patients exposed to corticosteroids were more likely to sustain fracture than non-exposed RA patients (5.7 vs. 2.4%, P<0.01). In addition, only when comparing patients exposed to corticosteroids, was there statistical evidence of an association between RA and an increased fracture rate (6.2 vs. 3.5%, P<0.05). CONCLUSION: Patients with RA exposed to corticosteroids are at high risk of fracture. Patients with RA had more bone fragility management than controls.

Development and Validation of a Predictive Model of Hypovitaminosis D in General Adult Population: SCOPYD Study.

The worldwide global increase in serum 25-hydroxyvitamin D (25(OH)D) measurements has led some countries to restrict reimbursement for certain clinical situations only. Another approach could consist in providing physicians with screening tools in order to better target blood test prescription. The objective of the SCOPYD study was to identify the best combination of predictors of serum VitD concentration among adults aged 18-70 years. Potential risk factors for VitD deficiency were collected using a comprehensive self-administered questionnaire. A multivariable linear regression was used to build a predictive model of serum 25(OH)D concentration. Among 2488 participants, 1080 (43.4%) had VitD deficiency (<50 nmol/L) and 195 (7.8%) had severe deficiency (<25 nmol/L). The final model included sunlight exposure in the preceding week and during the last holidays, month of blood sampling, age, sex, body mass index, skin phototype, employment, smoking, sport practice, latitude, and VitD supplementation in preceding year. The area under the curve was 0.82 (95% CI (0.78; 0.85)) for severe deficiency. The model predicted severe deficiency with a sensitivity of 77.9% (95% CI (69.1; 85.7)) and a specificity of 68.3% (95% CI (64.8; 71.9)). We identified a set of predictors of severe VitD deficiency that are easy to collect in routine that may help to better target patients for serum 25(OH)D concentration determination.

Refracture and mortality following hospitalization for severe osteoporotic fractures: The Fractos Study.

Severe osteoporotic fractures (hip, proximal humerus, pelvic, vertebral and multiple rib fractures) carry an increased risk of mortality. This retrospective cohort study in the French national healthcare database aimed to estimate refracture and mortality rates after severe osteoporotic fractures at different sites, and to identify mortality-related variables. A total of 356,895 patients hospitalized for severe osteoporotic fracture between 2009 and 2014 inclusive were analyzed. The cohort was followed for 2 to 8 years up to the study end or until the patient died. Data were extracted on subsequent hospitalizations, refracture events, treatments, comorbidities of interest and survival. Time to refracture and survival were described using Kaplan-Meier analysis by site of fracture and overall. Mortality risk factors were identified using a Cox model. Hip fractures accounted for 60.4% of the sample (N = 215,672). In the 12 months following fracture, 58,220 patients (16.7%) received a specific osteoporosis treatment, of whom 21,228 were previously treatment-naïve. The 12-month refracture rate was 6.3% (95% confidence interval [CI], 6.2%-6.3%), ranging from 4.0% (95% CI, 3.7%-4.3%) for multiple rib fractures to 7.8% (95% CI, 7.5%-8.1%) for pelvic fractures. Twelve-month all-cause mortality was 12.8% (95% CI, 12.7%-12.9%), ranging from 5.0% (95% CI, 4.7%-5.2%) for vertebral fractures to 16.6% (95% CI, 16.4%-16.7%) for hip fractures. Osteoporosis-related mortality risk factors included fracture site, previous osteoporotic fracture (hazard ratio 1.21; 95% CI, 1.18-1.23), hip refracture (1.74; 95% CI, 1.71-1.77), and no prior osteoporosis treatment (1.24; 95% CI, 1.22-1.26). Comorbid cancer (3.15; 95% CI, 3.09-3.21) and liver disease (2.54; 95% CI, 2.40-2.68) were also strongly associated with mortality. In conclusion, severe osteoporotic fractures, including certain non-hip nonvertebral fractures, carry a high burden in terms of mortality and refracture risk. However, most patients received no anti-osteoporotic treatment. The findings emphasize the importance of better management of patients with severe fractures, and of developing effective strategies to reduce fracture risk in patients with osteoporosis. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Second-generation hormonotherapy in prostate cancer and bone microenvironment.

Prostate cancer (Pca) is the most commonly diagnosed cancer affecting men in France. Before the age of 75 years old, 1 in 8 French men will have Pca. Androgen deprivation therapies (ADT) remain the standard of care. Such therapies induce significant bone loss. The bone-remodelling cycle depends on the androgen synthesis signalling pathways. Furthermore, age-specific hormonal decline plays a key role in the decrease in bone mass. As a result, the older the patients, the more likely they are to have osteoporosis if they are treated with hormone therapy. Their risk of osteoporotic fracture has an impact on their quality of life and their capacity of independent living. In recent years, newer hormone therapies (acetate abiraterone, enzalutamide, apalutamide and darolutamide) have proved efficient in metastatic castration-resistant Pca (mCRPC) patients as well as in hormone naïve patients, and actually in nonmetastatic diagnosis. The combination of these treatments with ADT highly inhibit androgen production pathways. They are prescribed to aged patients undergoing bone density loss after first-generation antiandrogen treatment. Specific recommendations for bone health management in Pca patients are currently lacking. To date, bone mineral density in patients treated with second-generation hormone therapy has never been assessed in a prospective study. This review aims at reviewing what is known about the impact of second-generation hormonotherapy on bone microenvironment.

Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry.

OBJECTIVE: To investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA). METHODS: We analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders. RESULTS: Of 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity. CONCLUSIONS: People with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.

COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study.

BACKGROUND: Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases. METHODS: In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609. FINDINGS: Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66-6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46-0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55-3·19, p=0·53). INTERPRETATION: Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases. FUNDING: None.

Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry.

OBJECTIVES: To determine factors associated with COVID-19-related death in people with rheumatic diseases. METHODS: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. RESULTS: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. CONCLUSION: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Part of pain labelled neuropathic in rheumatic disease might be rather nociplastic.

Pain in rheumatic diseases is primarily due to mechanical or inflammatory mechanism, but neuropathic pain (NP) component is also occurring in many conditions and is probably underdiagnosed. The purpose of this article is to provide an overview of prevalence, pathophysiological and currently available treatment of NP in rheumatic diseases. When associated with clinical evaluation assessing neurological clinical signs and neuroanatomical distribution, Douleur Neuropathique 4 Questions, painDETECT, Leeds assessment of neuropathic symptoms and signs and Neuropathic Pain Questionnaire can detect NP component. Inflammatory or connective diseases, osteoarthritis, back pain or persistent pain after surgery are aetiologies that all may have a neuropathic component. Unlike nociceptive pain, NP does not respond to usual analgesics such as paracetamol and non-steroidal anti-inflammatory drugs. Entrapment neuropathy, peripheral neuropathy or small-fibre neuropathy are different aetiologies that can lead to NP. A part of the pain labelled neuropathic is rather nociplastic, secondary to a central sensitisation mechanism. Identifying the right component of pain (nociceptive vs neuropathic or nociplastic) could help to better manage pain in rheumatic diseases with pharmacological and non-pharmacological treatments.

Skeletal muscle of females and males with constitutional thinness: a low intramuscular lipid content and oxidative profile.

Constitutional thinness (CT) is a nonpathological state of underweight. The current study aimed to explore skeletal muscle energy storage in individuals with CT and to further characterize muscle phenotype at baseline and in response to overfeeding. Thirty subjects with CT (15 females, 15 males) and 31 normal-weight control subjects (16 females, 15 males) participated in the study. Histological and enzymological analyses were performed on muscle biopsy specimens before and after overfeeding. In the skeletal muscle of CT participants compared with controls, we observed a lower content of intramuscular triglycerides for type I (-17%, p < 0.01) and type IIA (-14%, p < 0.05) muscle fibers, a lower glycogen content for type I (-6%, p < 0.01) and type IIA (-5%, p < 0.05) muscle fibers, a specific fiber-type distribution, a marked muscle hypotrophy (-20%, p < 0.001), a low capillary-to-fiber ratio (-19%, p < 0.001), and low citrate synthase activity (-18%, p < 0.05). In response to overfeeding, CT participants increased their intramuscular triglycerides content in type I (+10%, p < 0.01) and type IIA (+9%, p < 0.01) muscle fibers. CT individuals seem to present an unusual muscle phenotype and different adaptations to overfeeding compared with normal-weight individuals, suggesting a specific energy metabolism and muscle adaptations. ClinicalTrials.gov registration no. NCT02004821. Novelty Low intramuscular triglycerides and glycogen content in skeletal muscle of constitutionally thin individuals. Low oxidative capacity, low capillary supply, and fiber hypotrophy in skeletal muscle of constitutionally thin individuals. Increase in intramuscular triglycerides in constitutional thinness in response to overfeeding.

Resistance to lean mass gain in constitutional thinness in free-living conditions is not overpassed by overfeeding.

BACKGROUND: Constitutional thinness (CT), a non-malnourished underweight state with no eating disorders, is characterized by weight gain resistance to high fat diet. Data issued from muscle biopsies suggested blunted anabolic mechanisms in free-living state. Weight and metabolic responses to protein caloric supplementation has not been yet explored in CT. METHODS: A 2 week overfeeding (additional 600 kcal, 30 g protein, 72 g carbohydrate, and 21 g fat) was performed to compare two groups of CTs (12 women and 11 men) to normal-weight controls (12 women and 10 men). Bodyweight, food intake, energy expenditure, body composition, nitrogen balance, appetite hormones profiles, and urine metabolome were monitored before and after overfeeding. RESULTS: Before overfeeding, positive energy gap was found in both CT genders (309 ± 370 kcal in CT-F and 332 ± 709 kcal in CT-M) associated with higher relative protein intake per kilo (1.74 ± 0.32 g/kg/day in CT-F vs. 1.16 ± 0.23 in C-F, P < 0.0001; 1.56 ± 0.36 in CT-M vs. 1.22 ± 0.32 in C-M, P = 0.03), lower nitrogen (7.26 ± 2.36 g/day in CT-F vs. 11.41 ± 3.64 in C-F, P = 0.003; 9.70 ± 3.85 in CT-M vs. 14.14 ± 4.19 in C-M, P = 0.02), but higher essential amino acids urinary excretion (CT/C fold change of 1.13 for leucine and 1.14 for arginine) in free-living conditions. After overfeeding, CTs presented an accentuated positive energy gap, still higher than in controls (675 ± 540 in CTs vs. 379 ± 427 in C, P = 0.04). Increase in lean mass was induced in both controls genders but not in CTs (a trend was noticed in CT women), despite a similar nitrogen balance after overfeeding (5.06 ± 4.33 g/day in CTs vs. 4.28 ± 3.15 in controls, P = 0.49). Higher anorectic gut hormones' tone, glucagon-like peptide 1 and peptide tyrosine tyrosine, during test meal and higher snacking frequency were noticed before and after overfeeding in CTs. CONCLUSIONS: The blunted muscle energy mechanism, previously described in CTs in free-living state, is associated with basal saturated protein turn over suggested by the concordance of positive nitrogen balance and an increased urine excretion of several essential amino acids. This saturation cannot be overpassed by increasing this spontaneous high-protein intake suggesting a resistance to lean mass gain in CT phenotype.

Obesity, Bariatric Surgery, and Fractures.

CONTEXT: Obesity and its associated comorbidities are a recognized and growing public health problem. For a long time, obesity-associated effects on bone were considered to strengthen the bone, mainly because of the known relationship between body weight and bone mass and the long-term weight-bearing load effect on bone. However, recent epidemiologic studies have shown that obesity may not have a fully protective effect on the occurrence of fragility fractures. The goal of this article is to review updated information on the link between obesity, bariatric surgery, and fractures. METHODS: The primary source literature for this review was acquired by searching a published database for reviews and articles up to January 2018. Additional references were selected through the in-depth analysis of the relevant studies. RESULTS: We present data showing that overweight and obesity are often encountered in fracture cases. We also analyzed possible reasons and risk factors for fractures associated with overweight and patients with obesity. In addition, this review focuses on the complex effects of dramatic changes in body composition when interpreting dual-energy X-ray absorptiometry readings and findings. Finally, we review the data on the effects and consequences of bariatric surgery on bone metabolism and the risk of fractures in patients undergoing these procedures. CONCLUSION: Because of various adiposity-induced effects, patients with obesity are at risk for fracture in certain sites. Bariatric surgery increases the risk of fractures in patients undergoing malabsorptive procedures.

Prealbumin, platelet factor 4 and S100A12 combination at baseline predicts good response to TNF alpha inhibitors in rheumatoid arthritis.

OBJECTIVES: Tumour necrosis factor-alpha inhibitors (TNFi) are effective treatments for Rheumatoid Arthritis (RA). Responses to treatment are barely predictable. As these treatments are costly and may induce a number of side effects, we aimed at identifying a panel of protein biomarkers that could be used to predict clinical response to TNFi for RA patients. METHODS: Baseline blood levels of C-reactive protein, platelet factor 4, apolipoprotein A1, prealbumin, α1-antitrypsin, haptoglobin, S100A8/A9 and S100A12 proteins in bDMARD naive patients at the time of TNFi treatment initiation were assessed in a multicentric prospective French cohort. Patients fulfilling good EULAR response at 6 months were considered as responders. Logistic regression was used to determine best biomarker set that could predict good clinical response to TNFi. RESULTS: A combination of biomarkers (prealbumin, platelet factor 4 and S100A12) was identified and could predict response to TNFi in RA with sensitivity of 78%, specificity of 77%, positive predictive values (PPV) of 72%, negative predictive values (NPV) of 82%, positive likelihood ratio (LR+) of 3.35 and negative likelihood ratio (LR-) of 0.28. Lower levels of prealbumin and S100A12 and higher level of platelet factor 4 than the determined cutoff at baseline in RA patients are good predictors for response to TNFi treatment globally as well as to Infliximab, Etanercept and Adalimumab individually. CONCLUSION: A multivariate model combining 3 biomarkers (prealbumin, platelet factor 4 and S100A12) accurately predicted response of RA patients to TNFi and has potential in a daily practice personalized treatment.

Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model.

Periarticular bone loss in rheumatoid arthritis (RA) is considered to be mainly related to synovial inflammation. However, strong bone loss has also described at the time of arthritis onset. Recently, a paradoxical exacerbation of joint damage was described when blocking sclerostin in various arthritis models. Thus, we aimed to determine kinetics of bone loss and its mechanisms in the adjuvant induced arthritis (AIA) rat model of RA. AIA was induced (n = 35) or not (n = 35) at day 0. In addition to well-known arthritis at day 12, we showed with 3D-imaging and histomorphometry that bone microstructural alterations occurred early from day 8 post-induction, characterized by cortical porosity and trabecular bone loss. Active osteoclastic surfaces were increased from day 8 with RANKL upregulation. More surprisingly SOST and DKK1 were overexpressed from day 6 and followed by a dramatic decrease in bone formation from day 8. At the time of arthritis onset, SOST and DKK1 returned to control values, but frizzled related protein 1 (SFRP1), proinflammatory cytokines, and MMPs started to increase. Bone alterations before arthritis onset reinforce the hypothesis of an early bone involvement in arthritis. Kinetics of osteocyte markers expression should be considered to refine Wnt inhibitor treatment strategies.