Bone Outcomes Research Articles

Bone effects of metformin monotherapy and its combination with teneligliptin: A 12-week follow-up study in patients with type 2 diabetes mellitus

AimsThe skeletal effects of metformin monotherapy and in combination with teneligliptin are not well illustrated in patients with T2DM. To address this, we conducted an observational study to evaluate the effect of these oral hypoglycemic agents on bone turnover markers. MethodsWe recruited patients with T2DM and first-ever prescribed metformin monotherapy or metformin combined with teneligliptin from a tertiary care teaching hospital in New Delhi, North India. Both bone formation and resorption markers, IL-6 and PTD, were estimated along with glycated hemoglobin at baseline and 12 weeks. ResultsIn both groups, hbA1c levels decreased significantly from baseline to 12 weeks. In the metformin-treated group, β-CTX, sRANKL, IL-6, and PTD decreased significantly, and no significant changes were observed in P1NP, OC, BAP, or OPG at 12 weeks from baseline. In the metformin + teneligliptin group, BAP, β-CTX, sRANKL, IL-6, and PTD decreased significantly, and no significant changes were observed in P1NP, OC, or OPG after 12 weeks from baseline. ConclusionsThe positive bone outcome of metformin or teneligliptin was linked to bone resorption rather than bone formation and was independent of changes in HbA1c or PTD. However, these results must be confirmed with well-designed RCTs with more extended follow-up periods.

Clinical features and treatment outcomes of bone and joint nontuberculous mycobacterial infections according to immune status: a 9-year retrospective observational cohort

ObjectivesNontuberculous mycobacteria (NTM) bone and joint infections (BJIs) are uncommon. We evaluated the characteristics of BJIs and identified differences according to immune status. MethodsWe performed a multicenter retrospective study in France involving patients with documented NTM BJI over a 9-year period. We collected the clinical and microbiological characteristics, management, and clinical outcomes of the patients. ResultsOverall, 95 patients were included, of whom 50.5% (48/95) were immunosuppressed. Tenosynovitis was more frequent in the immunocompetent group, and native arthritis more common in the immunosuppressed group. Mycobacerium marinum and M. abscessus complex were significantly more frequent in the immunocompetent group, and M. avium and M. xenopi were significantly more frequent in the immunosuppressed group. The combination of antibiotherapy with surgery tended to be more frequent in the immunocompetent than the immunosuppressed group (63.8% (30/47) vs 47.8% (22/46), respectively); of the latter, 45.7% (21/46) received antimicrobial therapy alone, a higher frequency than in the immunocompetent group (23.4%, 11/47). The median duration of antimicrobial treatment was similar in the two groups (11 months). Mortality was significantly higher in the immunosuppressed group. ConclusionsAlthough the clinical presentations and the NTM species involved in BJI differed according to immune status, most recovered completely after treatment.

Trifocal versus Pentafocal bone transport in segmental tibial defects: a matched comparative analysis for posttraumatic osteomyelitis treatment

PurposeThe objective of this study was to evaluate and compare the effectiveness and clinical results of trifocal bone transport (TBT) and pentafocal bone transport (PBT) in treating distal tibial defects > 6 cm resulting from posttraumatic osteomyelitis, highlighting the potential advantages and challenges of each method.MethodsA retrospective assessment was conducted on an overall population of 46 eligible patients with distal tibial defects > 6 cm who received treatment between January 2015 and January 2019. Propensity score analysis was used to pair 10 patients who received TBT with 10 patients who received PBT. The outcomes assessed included demographic information, external fixation time (EFT), external fixation index (EFI), bone and functional outcomes assessed using the Association for the Study and Application of the Method of Ilizarov (ASAMI) scoring system, and postoperative complications evaluated using the Paley classification.ResultsThe demographic and baseline data of the two groups were comparable. Following radical debridement, the average tibial defect was 7.02 ± 0.68 cm. The mean EFT was significantly shorter in the PBT group (130.9 ± 16.0 days) compared to the TBT group (297.3 ± 14.3 days). Similarly, the EFI was lower in the PBT group (20.67 ± 2.75 days/cm) than in the TBT group (35.86 ± 3.69 days/cm). Both groups exhibited satisfactory postoperative bone and functional results. Pin site infection was the most common complication and the rates were significantly different between the groups, with the PBT group demonstrating a higher incidence.ConclusionBoth TBT and PBT effectively treat posttraumatic tibial defects greater than 6 cm, with PBT offering more efficient bone regeneration. However, PBT is associated with a higher rate of pin site infections, highlighting the importance of careful management in these complex procedures and emphasizing the need for expert surgical execution and tailored treatment approaches in orthopedic reconstructive surgery.

Impact of 10 years of conventional steroids vs dual-release hydrocortisone on metabolic, cardiovascular, and bone outcomes in treatment-naive patients with adrenal insufficiency

Impact of 10 years of conventional steroids vs dual-release hydrocortisone on metabolic, cardiovascular, and bone outcomes in treatment-naive patients with adrenal insufficiency

Improving the identification of bone-specific physical activity using wrist-worn accelerometry: A cross-sectional study in 11-12-year-old Australian children.

Physical activity (PA) during childhood and adolescence is important for the accrual of maximal peak bone mass. The precise dose that benefits bone remains unclear as methods commonly used to analyze PA data are unsuitable for measuring bone-relevant PA. Using improved accelerometry methods, this study identified the amount and intensity of PA most strongly associated with bone outcomes in 11-12-year-olds. Participants (n=770; 382 boys) underwent tibial peripheral quantitative computed tomography to assess trabecular and cortical density, endosteal and periosteal circumference and polar stress-strain index. Seven-day wrist-worn raw acceleration data averaged over 1-s epochs was used to estimate time accumulated above incremental PA intensities (50 milli-gravitational unit (mg) increments from 200 to 3000mg). Associations between time spent above each 50mg increment and bone outcomes were assessed using multiple linear regression, adjusted for age, sex, height, weight, maturity, socioeconomic position, muscle cross-sectional area and PA below the intensity of interest. There was a gradual increase in mean R2 change across all bone-related outcomes as the intensity increased in 50mg increments from >200 to >700mg. All outcomes became significant at >700mg (R2 change=0.6%-1.3% and p=0.001-0.02). Any further increases in intensity led to a reduction in mean R2 change and associations became non-significant for all outcomes >1500mg. Using more appropriate accelerometry methods (1-s epochs; no a priori application of traditional cut-points) enabled us to identify that ∼10min/day of PA >700mg (equivalent to running ∼10km/h) was positively associated with pQCT-derived measures of bone density, geometry and strength in 11-12-year-olds.

Radiographic and functional results of Ilizarov fixation in the management of nonunion of tibia and femur fractures: a retrospective case series.

Femoral and tibial fractures may result in delayed union and nonunion, posing significant challenges in orthopedic practice. The Ilizarov technique has emerged as a promising solution for managing these complex cases. Evaluate the radiographic and functional results of Ilizarov fixation in the treatment of nonunion of tibia and femur fractures. Retrospective. Hospitals affiliated with a university hospital. Patient demographics, fracture characteristics, and treatment details were analyzed for the period from October 2015 to September 2022 in patients who were treated for nonunion of the tibia and femur using the Ilizarov fixator. Clinical and radiological assessments were performed using the Association for the Study and Application of Methods of Ilizarov (ASAMI) criteria. The study focused on assessing the average duration for union and frame removal, bone results, successful union rates, and functional results using the ASAMI criteria, obtaining data from the existing medical records, spanning various medical facilities treating nonunion fractures. 126 patients. The average duration for union and frame removal was 8 months, with excellent bone results observed in 60.32% of cases. Out of 126 patients, 118 achieved successful union, while there were 2 failure cases necessitating amputation (1.52%). Functional results revealed excellent outcomes in 39.68% of cases. Complications included pin tract infections, ankle and knee stiffness, and limb shortening. External fixation duration and infection eradication were consistent with previous research, emphasizing the technique's effectiveness. The Ilizarov technique proved highly effective in managing nonunion tibia and femur fractures, offering favorable outcomes in terms of union, infection control, pain relief, and functional recovery. While excellent bone outcomes do not guarantee optimal function, this method remains a reliable approach for complex cases. Potential biases inherent in retrospective analyses and the need for further randomized controlled trials to comprehensively compare treatment modalities.

The integration of ortho-plastic limb salvage teams in the humanitarian response to violence-related open tibial fractures: evaluating outcomes in the Gaza Strip

BackgroundLimb salvage by ortho-plastic teams is the standard protocol for treating open tibial fractures in high-income countries, but there’s limited research on this in conflict settings like the Gaza Strip. This study assessed the clinical impact of gunshot-related open tibial fractures, compared patient management by orthopedic and ortho-plastic teams, and identified the risk factors for bone non-union in this context.MethodsA retrospective review of medical records was conducted on Gaza Strip patients with gunshot-induced-open tibial fractures from March 2018 to October 2020. Data included patient demographics, treatments, and outcomes, with at least one year of follow-up. Primary outcomes were union, non-union, infection, and amputation.ResultsThe study included 244 injured individuals, predominantly young adult males (99.2%) with nearly half (48.9%) having Gustilo-Anderson type IIIB fractures and more than half (66.8%) with over 1 cm of bone loss. Most patients required surgery, including rotational flaps and bone grafts with a median of 3 admissions and 9 surgeries. Ortho-plastic teams managed more severe muscle and skin injuries, cases with bone loss > 1 cm, and performed less debridement compared to other groups, though these differences were not statistically significant. Non-union occurred in 53% of the cases, with the ortho-plastic team having the highest rate at 63.6%. Infection rates were high (92.5%), but no significant differences in bone or infection outcomes were observed among the different groups. Logistic regression analysis identified bone loss > 1 cm, vascular injury, and the use of a definitive fixator at the first application as predictors of non-union.ConclusionsThis study highlights the severity and complexity of such injuries, emphasizing their significant impact on patients and the healthcare system. Ortho-plastic teams appeared to play a crucial role in managing severe cases. However, further research is still needed to enhance our understanding of how to effectively manage these injuries.

Skeletal parathyroid hormone hyporesponsiveness: a neglected, but clinically relevant reality in chronic kidney disease.

Defining the optimal parathyroid hormone (PTH) target in chronic kidney disease (CKD) is challenging, especially for bone outcomes, due to the substantial variability in the skeleton's response to PTH. Although PTH hyporesponsiveness is as integral a component of CKD-mineral bone disorder as elevated PTH levels, clinical awareness of this condition is limited. In this review, we will discuss factors and mechanisms contributing to PTH hyporesponsiveness in CKD. This knowledge may provide clues towards a personalized approach to treating secondary hyperparathyroidism in CKD. Indicates a link between disturbed phosphate metabolism and impaired skeletal calcium sensing receptor signaling as an important mediator of PTH hyporesponsiveness in CKD. Further, cohort studies with diverse populations point towards differences in mineral metabolism control, rather than genetic or environmental factors, as drivers of the variability of PTH responsiveness. Skeletal PTH hyporesponsiveness in CKD has a multifactorial origin, shows important interindividual variability, and is challenging to estimate in clinical practice. The variability in skeletal responsiveness compromises PTH as a biomarker of bone turnover, especially when considering populations that are heterogeneous in ethnicity, demography, kidney function, primary kidney disease and mineral metabolism control, and in patients treated with bone targeting drugs.

Bone health and physical activity in adolescents with juvenile idiopathic arthritis: a cross-sectional case-control study

BackgroundAdolescents with juvenile idiopathic arthritis (JIA) tend to engage in less physical activity than their typically developing peers. Physical activity is essential for bone development and reduced physical activity may detrimentally effect bone health. Thus, we examined differences in total body bone mineral content (BMC) and areal bone mineral density (aBMD) between adolescents with JIA and adolescent controls without JIA. We also examined associations between moderate-to-vigorous physical activity (MVPA), lean mass, and bone outcomes.MethodsParticipants included 21 adolescents with JIA (14 females, 7 males) and 21 sex- and age-matched controls aged 10–20 years. Assessments included: height; weight; triple-single-leg-hop distance (TSLH); MVPA by accelerometry; and total body BMC, aBMD, and lean mass measured using dual X-ray absorptiometry. Height-adjusted z-scores were calculated for BMC and aBMD and used for all analyses. Multiple linear mixed effects models examined group differences in BMC and aBMD, adjusting for sex, maturity, MVPA, TSLH, and lean mass. Participants clusters, based on sex and age (within 18 months), were considered random effects.ResultsAdolescents with JIA had lower total body aBMD z-scores [β (95% CI); -0.58 (-1.10 to -0.07), p = 0.03] and BMC z-scores [-0.47 (-0.91 to -0.03), p = 0.04] compared with controls. Mean daily MVPA was 22.0 min/day lower in adolescents with JIA than controls; however, MVPA was not associated with aBMD [-0.01 (-0.01 to 0.01), p = 0.32] or BMC [0.00 (-0.01 to 0.00), p = 0.39]. Lean mass was positively associated with aBMD [0.05 (0.01 to 0.09) g/cm2, p = 0.03] and BMC [0.06 (0.03 to 0.10) g, p < 0.001].ConclusionAdolescents with JIA had lower total body aBMD and BMC compared with sex- and age-matched controls without JIA. Group differences in bone outcomes were not associated with the lower MVPA participation of adolescents with JIA. Despite this, physical activity should still be encouraged as it promotes physical well-being.

Treatment of tibial bone defects caused by infection: a retrospective comparative study of bone transport using a combined technique of unilateral external fixation over an intramedullary nail versus circular external fixation over an intramedullary nail

BackgroundThe purpose of the study was to assess and compare the clinical efficacy of bone transport with either circular or unilateral external fixators over an intramedullary nail in the treatment of tibial bone defects caused by infection.MethodsBetween May 2010 and January 2019, clinical and radiographic data were collected and analyzed for patients with bone defects caused by infection. Thirteen patients underwent bone transport using a unilateral external fixator over an intramedullary nail (Group A), while 12 patients were treated with a circular external fixator over an intramedullary nail (Group B). The bone and functional outcomes of both groups were assessed and compared using the Association for the Study and Application of the Method of the Ilizarov criteria, and postoperative complications were evaluated according to the Paley classification.ResultsA total of 25 patients were successfully treated with bone transport using external fixators over an intramedullary nail, with a mean follow-up time of 31.63 ± 5.88 months. There were no significant statistical differences in age, gender, previous surgery per patient, duration of infection, defect size, and follow-up time between Group A and Group B (P > 0.05). However, statistically significant differences were observed in operation time (187.13 ± 21.88 min vs. 255.76 ± 36.42 min, P = 0.002), intraoperative blood loss (39.26 ± 7.33 mL vs. 53.74 ± 10.69 mL, P < 0.001), external fixation time (2.02 ± 0.31 month vs. 2.57 ± 0.38 month, P = 0.045), external fixation index (0.27 ± 0.08 month/cm vs. 0.44 ± 0.09 month/cm, P = 0.042), and bone union time (8.37 ± 2.30 month vs. 9.07 ± 3.12, P = 0.032) between Group A and Group B. The excellent and good rate of bone and functional results were higher in Group A compared to Group B (76.9% vs. 75% and 84.6% vs. 58.3%). Statistically significant differences were observed in functional results (excellent/good/fair/poor, 5/6/2/0 vs. 2/5/4/1, P = 0.013) and complication per patient (0.38 vs. 1.16, P = 0.012) between Group A and Group B.ConclusionsBone transport using a combined technique of external fixators over an intramedullary nail proved to be an effective method in treating tibial bone defects caused by infection. In comparison to circular external fixators, bone transport utilizing a unilateral external fixator over an intramedullary nail resulted in less external fixation time, fewer complications, and better functional outcomes.

Phenomewide Association Study of Health Outcomes Associated With the Genetic Correlates of 25 Hydroxyvitamin D Concentration and Vitamin D Binding Protein Concentration.

While it is known that vitamin D deficiency is associated with adverse bone outcomes, it remains unclear whether low vitamin D status may increase the risk of a wider range of health outcomes. We had the opportunity to explore the association between common genetic variants associated with both 25 hydroxyvitamin D (25OHD) and the vitamin D binding protein (DBP, encoded by the GC gene) with a comprehensive range of health disorders and laboratory tests in a large academic medical center. We used summary statistics for 25OHD and DBP to generate polygenic scores (PGS) for 66,482 participants with primarily European ancestry and 13,285 participants with primarily African ancestry from the Vanderbilt University Medical Center Biobank (BioVU). We examined the predictive properties of PGS25OHD, and two scores related to DBP concentration with respect to 1322 health-related phenotypes and 315 laboratory-measured phenotypes from electronic health records. In those with European ancestry: (a) the PGS25OHD and PGSDBP scores, and individual SNPs rs4588 and rs7041 were associated with both 25OHD concentration and 1,25 dihydroxyvitamin D concentrations; (b) higher PGS25OHD was associated with decreased concentrations of triglycerides and cholesterol, and reduced risks of vitamin D deficiency, disorders of lipid metabolism, and diabetes. In general, the findings for the African ancestry group were consistent with findings from the European ancestry analyses. Our study confirms the utility of PGS and two key variants within the GC gene (rs4588 and rs7041) to predict the risk of vitamin D deficiency in clinical settings and highlights the shared biology between vitamin D-related genetic pathways a range of health outcomes.

Leukocyte telomere length is associated with MRI-thigh fat-free muscle volume: data from 16 356 UK Biobank adults.

Telomere attrition may share common biological mechanisms with bone and muscle loss with aging. Here, we investigated the association between these hallmarks of aging using data from UK Biobank, a large observational study. Leukocyte telomere length (LTL as T/S ratio) was measured using a multiplex qPCR assay at baseline (2006-2010). Bone mineral density (whole body and regional; via dual-energy X-ray absorptiometry), trabecular bone score (via lumbar-spine dual-energy X-ray absorptiometry images), fat-free muscle volume (thighs; via magnetic resonance imaging), and muscle fat infiltration (thighs; via magnetic resonance imaging) were measured during the imaging visit (2014-2018). Regression models were used to model LTL against a muscle or bone outcome, unadjusted and adjusted for covariates. A total of 16356 adults (mean age: 62.8±7.5years, 50.5% women) were included. In the fully adjusted model, thigh fat-free muscle volume was associated with LTL in the overall sample (adjusted standardized β (aβ)=0.017, 95% CI 0.009 to 0.026, P<0.001, per SD increase in LTL), with stronger associations in men (aβ=0.022, 95% CI 0.010 to 0.034, P<0.001) than in women (aβ=0.013, 95% CI 0.000 to 0.025, P=0.041) (sex-LTL P=0.028). The adjusted odds ratio (aOR) for low thigh fat-free muscle volume (body mass index-adjusted, sex-specific bottom 20%) was 0.93 per SD increase in LTL (95% CI 0.89 to 0.96, P<0.001) in the overall sample, with stronger associations in men (aOR=0.92, 95% CI 0.87 to 0.99, P=0.008) than women (aOR=0.93, 95% CI 0.88 to 0.98, P=0.009), although the sex difference was not statistically significant in this model (sex-LTL P=0.37). LTL was not associated with bone mineral density, trabecular bone score, or muscle fat infiltration in the overall or subgroup analyses (P>0.05). LTL was consistently associated with thigh fat-free muscle volume in men and women. Future research should investigate moderating effects of lifestyle factors (e.g., physical activity, nutrition, or chronic diseases) in the association between LTL and muscle volume.

Scaphoid Fractures in Adults Aged 50 Years or Older: Epidemiology and Association With Osteopenia and Nonunion.

Scaphoid fractures are less commonly reported in adults older than 50 years. The association between bone density and outcomes following scaphoid fractures has not been explored in this patient population. The second metacarpal cortical percentage (2MCP) has been shown to predict low bone density. The purpose of this study is to describe the epidemiology and radiographic characteristics associated with scaphoid fractures in adults older than 50 years, determine the prevalence of osteopenia defined by 2MCP, and evaluate the characteristics associated with scaphoid nonunion in this population. We hypothesized that osteopenia defined by 2MCP would be common in this patient population and associated with scaphoid nonunion. Patients older than 50 years with an acute, closed scaphoid fracture were identified. Demographic data, radiographic characteristics, and outcome data were collected. The 2MCP was measured using standard hand radiographs. A total of 111 patients were identified. Most fractures were nondisplaced and occurred in women via low-energy mechanism. Fifty-six patients (50.5%) had osteopenia defined by a 2MCP less than 60%. Nondisplaced fractures achieved union faster than displaced fractures (P < .05). Displaced, unstable fractures were statistically associated with nonunion (P < .001). 2MCP did not correlate with nonunion. In adults older than 50 years, scaphoid fractures may represent a fragility fracture cohort given they occur more frequently in female patients via low-energy mechanisms and over half of the cohort had osteopenia defined by a 2MCP less than 60%. Displaced and unstable fractures were statistically more likely to go on to nonunion. Nonunion was not found to be associated with osteopenia.

Time-Restricted Eating and Bone Health: A Systematic Review with Meta-Analysis.

Time-restricted eating (TRE) has emerged as a dietary strategy that restricts food consumption to a specific time window and is commonly applied to facilitate weight loss. The benefits of TRE on adipose tissue have been evidenced in human trials and animal models; however, its impact on bone tissue remains unclear. To systematically synthesize and examine the evidence on the impact of TRE on bone health (bone mineral content (BMC), bone mineral density (BMD), and bone turnover factors), PubMed, Scopus, Cochrane CENTRAL, and Web of Science databases were systematically explored from inception to 1 October 2023 searching for randomized controlled trials (RCTs) aimed at determining the effects of TRE on bone health in adults (≥18 years). The Cochrane Handbook and the PRISMA recommendations were followed. A total of seven RCTs involving 313 participants (19 to 68 years) were included, with an average length of 10.5 weeks (range: 4 to 24 weeks). Despite the significant weight loss reported in five out of seven studies when compared to the control, our meta-analysis showed no significant difference in BMD (g/cm2) between groups (MD = -0.009, 95% CI: -0.026 to 0.009, p = 0.328; I2 = 0%). BMC and bone turnover markers between TRE interventions and control conditions were not meta-analyzed because of scarcity of studies (less than five). Despite its short-term benefits on cardiometabolic health, TRE did not show detrimental effects on bone health outcomes compared to those in the control group. Nevertheless, caution should be taken when interpreting our results due to the scarcity of RCTs adequately powered to assess changes in bone outcomes.

Genome-wide association study of osteoporosis identifies genetic risk and interactions with Dietary Approaches to Stop Hypertension diet and sugar-sweetened beverages in a Hispanic cohort of older adults.

Osteoporosis (OP) and low bone mass can be debilitating and costly conditions if not acted on quickly. This disease is also difficult to diagnose as the symptoms develop unnoticed until fracture occurs. Therefore, gaining understanding of the genetic risk associated with these conditions could be beneficial for health-care professionals in early detection and prevention. The Boston Puerto Rican Osteoporosis (BPROS) study, an ancillary study to the Boston Puerto Rican Health Study (BPRHS), collected information regarding bone and bone health. All bone measurements were taken during regular BPROS visits using dual-energy X-ray absorptiometry. The OP was defined as T-score ≤ -2.5 (≥2.5 SDs below peak bone mass). Dietary variables were collected at the second wave of the BPRHS via a food frequency questionnaire. We conducted genome-wide associations with bone outcomes, including BMD and OP for 978 participants. We also examined the interactions with dietary quality on the relationships between genotype and bone outcomes. We further tested if candidate genetic variants described in previous GWAS on OP and BMD contribute to OP risk in this population. Four variants were associated with OP: rs114829316 (IQ motif containing J gene), rs76603051, rs12214684 (melanin-concentrating hormone receptor 2 gene), and rs77303493 (Ras and Rab interactor 2 gene), and 2 variants were associated with BMD of lumbar spine (rs11855618, cingulin-like 1 gene) and hip (rs73480593, NTRK2), reaching the genome-wide significance threshold of P≤ 5E-08. In a gene-diet interaction analysis, we found that 1 SNP showed a significant interaction with the overall Dietary Approaches to Stop Hypertension (DASH) score, and 7 SNPs with sugar-sweetened beverages (SSBs), a major contributor to the DASH score. This study identifies new genetic markers related to OP and BMD in older Hispanic adults. Additionally, we uncovered unique genetic markers that interact with dietary quality, specifically SSBs, in relation to bone health. These findings may be useful to guide early detection and preventative care.

Efficacy of allogenic bone block graft in maxillary alveolar ridge reconstruction: A systematic review.

The purpose of this systematic review was to assess the efficiency of allogenic bone block grafts for maxillary alveolar ridge reconstruction. An electronic literature search was conducted using the PubMed, Cochrane Library, and Google Scholar databases. In addition, manual searching was done. Randomized controlled trials (RCTs) and prospective clinical trials (non-RCTs) up to December 2022, presenting the outcomes of allogenic bone blocks in maxillary alveolar ridge reconstruction, were identified. The rate of resorption, survival rate of implants, and formation of new bone following ridge augmentation were the outcome parameters. The quality assessment of the studies included was done using Joanna Briggs Institute Critical Appraisal Tool. A total of 13 studies that matched the inclusion criteria were included. The average rate of bone resorption ranged from 0.2 to 29.2 mm, with an implant survival rate of 96.87% across the included investigations. On an average, 25.83 mm (18.6-33/mm) of new mature compact osseous tissue was discovered, including viable osteocytes in close contact with the remnant cancellous bone. According to the results of the current systematic review, using allogenic bone block graft for reconstruction of atrophic maxillae appears to be an effective and reliable bone substitute for reconstruction of atrophic maxillae.

Induced membrane technique with plate fixation has a lower complication rate than bone transport over a plate for segmental tibial defects larger than 5cm.

The treatment of segmental tibial bone defects remains a surgical challenge. While Bone Transport (BT) and Induced Membrane Technique (IMT) are effective strategies for regenerating bone, there are few comparative studies between them. This investigation undertakes a comparative analysis of BT and IMT for large segmental tibial defects stabilised through plate fixation. Patients with segmental tibial defects exceeding 5cm were prospectively enrolled from 2008 to 2021 in a single institution, with a minimum follow-up duration of two years. All patients underwent either BT or IMT with plate fixation of the tibia. Procedural success, primary union as well as bone and functional outcome scores were compared. Complications, including non-unions, joint contractures and deep infections requiring surgical intervention, were also compared. 41 patients were recruited in total. 28 patients underwent Bone Transport Over a Plate (BTOP), while 13 patients underwent IMT with Plate fixation (IMTP). The procedural success rate trended higher in IMTP compared to BTOP (100% vs. 85.7%). The primary union rate also trended higher in IMTP compared to BTOP (92.3% vs. 79.2%). BTOP and IMTP achieved similar rates of satisfactory bone outcome scores (78.6% vs. 84.6%) and functional outcome scores (75% vs. 76.5%). There was no statistical difference between procedural success, primary union, bone and functional outcome scores. The complication rate in BTOP was 78.6% (22 of 28), including five docking site or regenerate non-unions, eight deep infections and nine joint contractures. IMTP had a 38.5% (5 of 13) complication rate, including one non-union, two deep infections and two joint contractures. The complication rate was 2.04 times higher in BTOP compared to IMTP (p = 0.0117). BTOP and IMTP are both equally effective techniques for regenerating bone in large tibial bone defects. However, IMTP may be a safer procedure than BTOP, with a lower probability of requiring additional procedures to address complications.

P383 Chronic Recurrent Multifocal Osteomyelitis associated with Paediatric Inflammatory Bowel disease: A Multi-Center Retrospective Study from the Paediatric IBD Porto Group of ESPGHAN

Abstract Background Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a rare, autoinflammatory bone disorder. CRMO was linked with inflammatory bowel disease (IBD), either as an extra intestinal manifestation or as a paradoxical effect of anti-TNFa therapy. Our goal was to define the clinical features and natural history of patients carrying a dual diagnosis of CRMO and IBD Methods Medical records of pediatric patients with a dual diagnosis of IBD and CRMO were reviewed in nineteen centers from the Paediatric IBD Porto Group of ESPGHAN. Collected data included demographic characteristics, disease features, laboratory studies, bone imaging findings and outcomes of each disease Results Forty five patients (21 [47%] females) with a diagnosis of CRMO and IBD (32 [71%] with Crohn’s disease) were included. Median age at the time of dual diagnosis was was 10.2 (IQR 12-13.5) years. Patients were divided into 3 groups, based on whether CRMO developed before, during or after IBD diagnosis. In 15 patients (33%), CRMO was diagnosed ±3 months from the time of IBD diagnosis, with 8 (53%) and 2 (13%) exhibiting mild and moderate-severe IBD activity, respectively. In 20 children (44%) IBD preceded CRMO diagnosis by &amp;gt;3 months with a median time of 238 (85-344) weeks. At the time of dual diagnosis, 12 (60%) patients were in IBD remission and 5 (25%) exhibited moderate-severe disease activity; however, CRP and ESR were elevated (1.5 [0.4-3.4] mg/dL and 35 [21-55] mm/h, respectively) while median fecal calprotectin was 567 (68-1800) mcg/gr, including 4 patients &amp;lt;100 mcg/gr. 17 patients (85%) were on anti-TNFa medication at the time CRMO developed. In 10 (22%) patients CRMO preceded the diagnosis of IBD (&amp;gt;3 months before IBD evolution) with a median time 46 (25-248) weeks. At time of IBD presentation, CRMO was in remission in 5 patients (50%). 4 patients were diagnosed with IBD, despite the lack of any abnormal gastro-intestinal symptoms. In patients in which CRMO was diagnosed after or during IBD diagnosis, different therapeutic regimens were used, including anti-TNFa agents, methotrexate, ustekinumab, NSAID’s and corticosteroids. Two patients also received bisphosphonates. In patients in which CRMO was diagnosed after or during IBD diagnosis, CRMO remission, defined as lack of bone pain, was achieved in 22.2 (15-51.8) weeks. CRMO complications occurred in 4 patients and included vertebral collapse, length discrepancy, bone fracture and bone deformity Conclusion In the largest cohort to date, CRMO presentation was not necessarily related to clinically active intestinal inflammation and could present before, during or after IBD diagnosis. CRMO remission was achieved in all patients; Nevertheless, a small number of patients developed significant bone complications

Advanced glycation end products are not associated with bone mineral density, trabecular bone score, and bone turnover markers in adults with and without type 1 diabetes: a cross-sectional study.

It is unclear if AGEs are involved in the bone fragility of type 1 diabetes (T1D). We evaluated whether skin AGEs by skin autofluorescence and serum AGEs (pentosidine, carboxymethyl-lysine [CML]) are independently associated with BMD by DXA (lumbar spine, hip, distal radius), trabecular bone score (TBS), serum bone turnover markers (BTMs: CTX; P1NP; osteocalcin), and sclerostin in participants with and without T1D. Linear regression models were used, with interaction terms to test effect modification by T1D status. In participants with T1D, correlations between skin and serum AGEs as well as between AGEs and 3-year HbA1C were evaluated using Spearman's correlations. Data are mean ± SD or median (interquartile range). We included individuals who participated in a cross-sectional study and had BMD and TBS assessment (106 T1D/65 controls, 53.2% women, age 43 ± 15yr, BMI 26.6 ± 5.5kg/m2). Participants with T1D had diabetes for 27.6 ± 12.3yr, a mean 3-yr HbA1C of 7.5 ± 0.9% and skin AGEs of 2.15 ± 0.54 arbitrary units. A subgroup of 65 T1D/57 controls had BTMs and sclerostin measurements, and those with T1D also had serum pentosidine (16.8[8.2-32.0] ng/mL) and CML [48.0 ± 16.8] ng/mL) measured. Femoral neck BMD, TBS, and BTMs were lower, while sclerostin levels were similar in participants with T1D vs controls. T1D status did not modify the associations between AGEs and bone outcomes. Skin AGEs were significantly associated with total hip and femoral neck BMD, TBS, BTMs, and sclerostin before, but not after, adjustment for confounders. Serum AGEs were not associated with any bone outcome. There were no significant correlations between skin and serum AGEs or between AGEs and 3-yr HbA1C. In conclusion, skin and serum AGEs are not independently associated with BMD, TBS, BTMs, and sclerostin in participants with relatively well-controlled T1D and participants without diabetes.

Genetic susceptibility and late bone outcomes in childhood acute lymphoblastic leukemia survivors.

Childhood acute lymphoblastic leukemia (cALL) survivors are at increased risk for bone comorbidities, but accurate screening tools for such comorbidities are limited. Polygenic scores (PGS) could stratify cALL survivors for risk of long-term adverse bone outcomes. We evaluated 214 (51% female) cALL survivors from the Prévenir les Effets TArdifs de la LEucémie study (median age 21yr). Bone mineral density (BMD) measurements were obtained using dual X-ray absorptiometry at the lumbar spine (LS-BMD), femoral neck (FN-BMD), and total body (TB-BMD), and vertebral fractures (VF) were documented using the vertebral deformity criterion. We computed a PGS for adult heel quantitative ultrasound speed of sound (gSOS), known to be associated with the risk of osteoporotic fracture, using imputed genotype data of the participants, and tested it for association with BMD Z-scores and VF risk, adjusting for clinical risk factors, and in sex and prognostic risk-stratified analyses. We found that a gSOS below the mean was associated with lower BMD in all three sites in univariate and multivariate models. In univariate analyses, 1 SD increase in gSOS conferred a 0.16 SD increase in LS-BMD (95% CI 0.005-0.31), whereas a gSOS above the mean was associated with a 0.31 SD higher LS-BMD (95% CI 0.008-0.61), a 0.36 SD higher TB-BMD (95% CI 0.06-0.67), and a 0.43 SD higher FN-BMD (95% CI 0.13-0.72). Models combining gSOS with clinical risk factors explained up to 16% of the variance of BMD phenotypes and obtained an area under the receiver operating characteristic curve for VF of 0.77 in subgroup analyses. Cranial radiation, high cumulative glucocorticoid doses, high risk group, and male sex were significant risk factors for lower BMD Z-scores. In conclusion, a PGS, in combination with clinical risk factors, could be used as a tool to risk stratify cALL survivors for treatment-related bone morbidity.