521 Incidence of Bone Fracture Rate Post-Burn and Trauma in Role 2 and 3 Treatment Centers

Introduction One of the hallmarks of critical illness and trauma is that it triggers resorptive bone loss, as well as an increase in bone fractures and a reduction in bone density. Sustained markers of bone resorption, bone formation, and regulators of bone signaling pathways are linked to prolonged inflammatory activities and the prolonged deterioration of bone microstructure. The objective of this study is to evaluate the bone fracture rate of the U.S Military, non-U.S. Military, North Atlantic Treaty Organization (NATO) Military, local civilian, and Coalition Forces population in Operation Enduring Freedom and Operation Freedom’s Sentinel with burns from 2005 to 2018 using the Department of Defense Trauma Registry (DoDTR; n=28,707). Our hypothesis is that there is a direct relationship between burn injury severity and bone fracture rates. Methods Pearson’s correlation coefficient and scatterplots were used in this retrospective, observational study to demonstrate the correlation between total body surface area (TBSA) burn and number of fractures by anatomical location. Results Approximately 15,195 patients (age: 26 ± 10 years) in Role 2 and Role 3 treatment centers reported fractures. Of those patients, 351 suffered from burns with 632 anatomical fracture locations. Facial fractures were most prominent (16%), followed by foot (12%), skull (12%), tibia/fibula (11%), hand (11%), and ulna/radius (10%). There was no initial correlation between n increasing severity of TBSA burn and count of fracture locations (ρ=-0.03, p=0.8572). Conclusions There was no acute correlation between burn severity and bone fracture rates; however, further analyses are required to assess chronic post-burn fracture rates.

Bone turnover and metabolite responses to exercise in people with and without long-duration type 1 diabetes: a case–control study

IntroductionExercise acutely alters markers of bone resorption and formation. As risk of fracture is increased in patients with type 1 diabetes, understanding if exercise-induced bone turnover is affected within this population is prudent. We assessed bone turnover responses to acute exercise in individuals with long-duration type 1 diabetes and matched controls.Research design and methodsParticipants with type 1 diabetes (n=15; age: 38.7±13.3; glycosylated hemoglobin: 60.5±6.7 mmol/mol; diabetes duration: 19.3±11.4 years) and age-matched, fitness-matched, and body mass index-matched controls (n=15) completed 45 min of incline walking (60% peak oxygen uptake). Blood samples were collected at baseline and immediately, 30 min, and 60 min postexercise. Markers of bone resorption (β-C-terminal cross-linked telopeptide of type 1 collagen, β-CTx) and formation (procollagen type-1 amino-terminal propeptide, P1NP), parathyroid hormone (PTH), phosphate, and calcium (albumin-adjusted and ionized) were measured. Data (mean±SD) were analyzed by a mixed-model analysis of variance.ResultsBaseline concentrations of P1NP and β-CTx were comparable between participants with type 1 diabetes and controls. P1NP did not change with exercise (p=0.20) but β-CTx decreased (p<0.001) in both groups, but less so in participants with type 1 diabetes compared with controls (−9.2±3.7%; p=0.02). PTH and phosphate increased immediately postexercise in both groups; only PTH was raised at 30 min postexercise (p<0.001), with no between-group differences (p>0.39). Participants with type 1 diabetes had reduced albumin and ionized calcium at all sample points (p<0.01).ConclusionsFollowing exercise, participants with type 1 diabetes displayed similar time-course changes in markers of bone formation and associated metabolites, but an attenuated suppression in bone resorption. The reduced albumin and ionized calcium may have implications for future bone health. Further investigation of the interactions between type 1 diabetes, differing modalities and intensities of exercise, and bone health is warranted.

THU0402 SERUM MARKERS OF BONE RESORPTION, FORMATION, AND MINERALIZATION DURING 8 YEARS OF TNF-Α BLOCKING THERAPY IN PATIENTS WITH ANKYLOSING SPONDYLITIS

Background:Ankylosing spondylitis (AS) is a chronic inflammatory disease, characterized by both excessive bone formation and bone loss. The bone turnover marker (BTM) bone-specific alkaline phosphatase (BALP) plays a central role in bone mineralization. Our previous study demonstrated that 3 years of TNF-α blocking therapy results in a significant increase in BALP.1However, longer follow-up is needed to investigate whether BALP stays elevated during TNF-α blocking therapy and also to explore the course of other BTM, osteocalcin (OC), procollagen type 1 N-terminal peptide (PINP) and serum type 1 collagen C-telopeptide (sCTX) in AS.Objectives:To evaluate serum markers of bone resorption, formation, and mineralization during 8 years of TNF-α blocking therapy in AS patients.Methods:Included were consecutive AS outpatients from the University Medical Center Groningen (UMCG) attending the Groningen-Leeuwarden Axial SpA (GLAS) cohort and who were treated with a maximum of 2 TNF-α blockers for at least 8 years. Patients were excluded when they used bisphosphonates at baseline or during follow-up. Data for a specific visit was coded as missing when patients either had experienced a fracture or received systemic corticosteroids within 1 year of that particular visit. Clinical and laboratory measurements were performed at baseline (before start of TNF-α blocking therapy), 3 and 6 months as well as 1, 2, 4, 6 and 8 years. Markers of bone formation OC, PINP and BALP, and marker of bone resorption sCTX were measured in serum. Z-scores of BTM were calculated using matched 10-years-cohorts of a Dutch reference group to correct for the normal influence that age and gender have on bone turnover. Serum levels of 25-hydroxyvitamin D (25(OH)D3) were assessed yearly. Generalized estimating equations were used to analyze BTM Z-scores over time within patients. Simple contrast was used to compare follow-up visits to baseline. P-values <0.05 were considered statistically significant.Results:In total, 37 AS patients were analyzed; 62% were male, 86% HLA-B27+, mean age was 38.6 ± 10.4 years, median symptom duration 14 years (IQR 10-25), median CRP 13 mg/L (IQR 6-25), and 30% had low vitamin 25(OH)D3 status (<50) at baseline. 35% of patients switched to a second TNF-α inhibitor during follow-up. ASDASCRPimproved significantly during treatment, from mean 3.8 ± 0.9 at baseline to 1.9 ± 0.9 after 8 years of follow-up (P<0.001). 25(OH)D3 levels were stable at group level, median 58 nmol/L (IQR 45-70) at baseline and 60 nmol/L (IQR 50-70) after 8 years. Bone regulation marker OC Z-score was found to be significantly increased only after 3 months of TNF-α blocking therapy compared to baseline. No significant changes during follow-up were found for collagen resorption marker sCTX Z-score. Collagen formation marker PINP Z-score was significantly increased after 3 and 6 months as well as 2 years of TNF-α blocking therapy. Bone mineralization marker BALP Z-score was significantly increased at all time points up to and including 2 years and returned to baseline levels during 4 to 8 years of TNF-α blocking therapy (Figure 1).Conclusion:In this subgroup of AS patients with established and active disease responding to TNF-α blocking therapy, we observed that the bone turnover balance favored bone formation during the first years of TNF-α blocking therapy, which corresponds to previously reported improvement in bone mineral density, especially at the lumbar spine.1New finding of our study is that after 8 years of treatment, markers of bone resorption, formation, and mineralization were all comparable to baseline values.References:[1]Arends et al. Arthritis Res Ther. 2012;14(2):R98Disclosure of Interests: :Mark Siderius: None declared, Anneke Spoorenberg: None declared, Suzanne Arends Grant/research support from: Grant/research support from Pfizer

Identification of metastasis in the skeleton bones in patients with breast and prostate cancer: markers of bone metabolism and MRI diagnostics

The purpose of the investigation is to study biochemical markers of bone metabolism in patients with breast cancer and prostate cancer during periods of stable remission and recurrence/metastasis and to assess their informative value in the diagnosis and monitoring of skeletal lesions. The study included 21 female patients with breast cancer and 18 male patients with prostate cancer. The start of monitoring is at least 3 years after complete tumor regression as a result of treatment: breast cancer – radical mastectomy, prostate cancer – radical prostatectomy. Markers of bone resorption (urine deoxypyridinoline, C-terminal telopeptide and tartrate-resistant acid phosphatase of blood serum) and osteogenesis (bone alkaline phosphatase and osteocalcin of blood serum) in patients with breast cancer and prostate cancer can be used for early diagnosis of metastasis in the skeleton bones: changes in indicators are observed 6-10 months before the first radiological/ MRI signs appear. The application of simultaneously used markers of bone resorption and osteogenesis in patients with breast cancer and prostate cancer provides a sensitivity of 89.7 %, a specificity of 84.5 %, a positive predictive value of 82.6 % and a negative predictive value of 95.3 %.