Secondary osteoporosis prevention: three-year outcomes from a Fracture Liaison Service in elderly hip fracture patients.

BACKGROUND: Hip fractures are the most serious fragility fractures due to their associated disability, higher hospitalization costs and high mortality rates. Fracture Liaison Service (FLS) programs have enhanced the management of osteoporosis-related fractures and have shown their clinical effectiveness. AIMS: To analyze the effect of the implementation of a FLS model of care over the survival and mortality rates following a hip fracture. METHODS: We conducted a prospective cohort study on patients over 60 years of age who suffered a hip fracture before and after the implementation of the FLS in our center (between January 2016 and December 2019). Patients were followed for three years after the index date. Mortality, complications and refracture rates were compared between the two groups using a Multivariate Cox proportional hazard model. RESULTS: A total of 1366 patients were included in this study (353 before FLS implementation and 1013 after FLS implementation). Anti-osteoporotic drugs were more frequently prescribed after FLS implementation (79.3% vs 12.5%; p < 0.01) and there was an increase in adherence to treatment (51.7% vs 30.2%; p < 0.01). A total of 413 (40.8%) patients after FLS implementation and 141 (39.9%) individuals before (p = 0.47) died during the three-years follow-up period. A second fracture occurred in 101 (10.0%) patients after FLS implementation and 37 (10.5%) individuals before (p = 0.78). Patients after the implementation of the FLS protocol had a lower all cause one-year mortality [adjusted Hazard Ratio (HR) 0.74 (0.57-0.94)] and a decreased risk of suffering a second osteoporotic fracture [adjusted HR 0.54 (0.39-0.75) in males and adjusted HR 0.46 (0.30-0.71) in females]. CONCLUSIONS: The implementation of a FLS protocol was associated with a lower all-cause one-year mortality rate and a higher survivorship in elderly hip fracture patients. However, no three-year mortality rate differences were observed between the two groups. We also found a reduction in the complication and second-fracture rates.

The Use of ß-Blockers and the Risk of Undergoing a Knee Arthroplasty: A Nested Case-Control Study.

BACKGROUND: Research has indicated that ß-blockers may downregulate various inflammatory mediators that are involved in osteoarthritis (OA). The objective of this study was to analyze the likelihood of total knee arthroplasty (TKA) among patients with OA who were being treated with ß-blockers. METHODS: A nested case-control study was conducted with use of clinical records from our institutional database. We included patients who attended our outpatient clinic with a history of new-onset knee pain between 2010 and 2019. The case group included individuals who had undergone primary TKA between 2018 and 2019, whereas the control group included subjects who had not undergone TKA. Controls were matched by date of birth ±2 years, sex, calendar time (first outpatient visit ±1 year), and the grade of arthritis; the control-to-case ratio was 1:1. Adherence to ß-blocker use was measured with use of the proportion of days covered (PDC) (i.e.,<0.25, ≥0.25 to <0.75, ≥0.75), and the cumulative effect was measured on the basis of the total number of years of treatment with ß-blockers. A binary logistic regression analysis adjusted to potential confounders was carried out to assess the risk of TKA associated with the intake of ß-blockers. RESULTS: A total of 600 patients were included (300 in the case group and 300 in the control group). Compared with non-users, any use of ß-blockers during the follow-up period was associated with a reduction in the likelihood of undergoing TKA (adjusted odds ratio [OR], 0.51; 95% confidence interval [CI], 0.34-0.77). The adjusted ORs for the use of selective ß1-blockers and nonselective ß1-blockers were 0.69 (95% CI, 0.36 to 1.31) and 0.42 (95% CI, 0.24 to 0.70), respectively. The adjusted ORs for any recent use, PDC of <0.25, PDC of ≥0.25 to <0.75, and PDC of ≥0.75 were 0.65 (95% CI, 0.51 to 0.99), 0.62 (95% CI, 0.21 to 1.85), 0.32 (95% CI, 0.09 to 1.22), and 0.55 (95% CI, 0.34 to 0.88), respectively. Regarding the cumulative effect of ß-blockers, the adjusted ORs for the use for <1 year, ≥1 to <5 years, and ≥5 years were 0.41 (95% CI, 0.20 to 0.85), 0.52 (95% CI, 0.21 to 1.33), and 0.36 (95% CI, 0.22 to 0.60), respectively. CONCLUSIONS: The use of nonselective ß-blockers was associated with a lower likelihood of undergoing TKA. Patients treated for prolonged periods were at a lower likelihood for undergoing TKA. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Non-union and use of proton pump inhibitors in the treatment of femoral and tibial shaft fractures: a nested case-control study.

BACKGROUND: Proton pump inhibitors (PPIs) are one of the most frequently used drugs worldwide. Previous research has shown that they could increase the risk of fracture and interfere with the fracture healing process. In this study, we analyzed the effect of PPIs on the risk of fracture non-union in patients with femoral and tibial shaft fractures. METHODS: A case-control study was conducted at our institution, including a total of 254 patients who underwent fixation surgery for a femoral or tibial shaft fracture between January 2012 and December 2017. We defined cases as patients who experienced a delayed union (case group A; n = 44), or non-union (cases group B; n = 12). Cases were matched by age, sex, and fractured bone, to 144 controls who did not experience delayed fracture union and did not require further procedures. A conditional logistic regression analysis was performed adjusted to potential confounders, and to the proportion of days covered (PDC) with PPIs. RESULTS: Adjusted ORs (95% CI) for undergoing a nail dynamization following a tibial or femoral shaft fracture were 1.38 (0.70-2.65) for any use PPIs. Patients with a longer PPI treatment courses (PDC ≥ 0.5) had an adjusted OR of 1.86 (0.70-4.76) for undergoing nail dynamization when compared with controls. Contrastingly, patients with a PDC < 0.5 had an adjusted OR of 1.03 (0.43-2.48). The adjusted OR (95% CI) for undergoing additional surgical procedures due to non-union was 4.5 (0.62-32.8) for any use of PPIs, and 12.3 (1.9-81.0) in patients with a PDC ≥ 0.5. CONCLUSIONS: A prolonged use of PPIs use was associated with a higher risk of fracture non-union in tibial and femoral shaft fractures.

Histological, Biomechanical, and Biological Properties of Genipin-Crosslinked Decellularized Peripheral Nerves.

Acellular nerve allografts (ANGs) represent a promising alternative in nerve repair. Our aim is to improve the structural and biomechanical properties of biocompatible Sondell (SD) and Roosens (RS) based ANGs using genipin (GP) as a crosslinker agent ex vivo. The impact of two concentrations of GP (0.10% and 0.25%) on Wistar rat sciatic nerve-derived ANGs was assessed at the histological, biomechanical, and biocompatibility levels. Histology confirmed the differences between SD and RS procedures, but not remarkable changes were induced by GP, which helped to preserve the nerve histological pattern. Tensile test revealed that GP enhanced the biomechanical properties of SD and RS ANGs, being the crosslinked RS ANGs more comparable to the native nerves used as control. The evaluation of the ANGs biocompatibility conducted with adipose-derived mesenchymal stem cells cultured within the ANGs confirmed a high degree of biocompatibility in all ANGs, especially in RS and RS-GP 0.10% ANGs. Finally, this study demonstrates that the use of GP could be an efficient alternative to improve the biomechanical properties of ANGs with a slight impact on the biocompatibility and histological pattern. For these reasons, we hypothesize that our novel crosslinked ANGs could be a suitable alternative for future in vivo preclinical studies.

Improving the regenerative microenvironment during tendon healing by using nanostructured fibrin/agarose-based hydrogels in a rat Achilles tendon injury model.

AIMS: Achilles tendon injuries are a frequent problem in orthopaedic surgery due to their limited healing capacity and the controversy surrounding surgical treatment. In recent years, tissue engineering research has focused on the development of biomaterials to improve this healing process. The aim of this study was to analyze the effect of tendon augmentation with a nanostructured fibrin-agarose hydrogel (NFAH) or genipin cross-linked nanostructured fibrin-agarose hydrogel (GP-NFAH), on the healing process of the Achilles tendon in rats. METHODS: NFAH, GP-NFAH, and MatriDerm (control) scaffolds were generated (five in each group). A biomechanical and cell-biomaterial-interaction characterization of these biomaterials was then performed: Live/Dead Cell Viability Assay, water-soluble tetrazolium salt-1 (WST-1) assay, and DNA-released after 48 hours. Additionally, a complete section of the left Achilles tendon was made in 24 Wistar rats. Animals were separated into four treatment groups (six in each group): direct repair (Control), tendon repair with MatriDerm, or NFAH, or GP-NFAH. Animals were euthanized for further histological analyses after four or eight weeks post-surgery. The Achilles tendons were harvested and a histopathological analysis was performed. RESULTS: Tensile test revealed that NFAH and GP-NFAH had significantly higher overall biomechanical properties compared with MatriDerm. Moreover, biological studies confirmed a high cell viability in all biomaterials, especially in NFAH. In addition, in vivo evaluation of repaired tendons using biomaterials (NFAH, GP-NFAH, and MatriDerm) resulted in better organization of the collagen fibres and cell alignment without clinical complications than direct repair, with a better histological score in GP-NFAH. CONCLUSION: In this animal model we demonstrated that NFAH and GP-NFAH had the potential to improve tendon healing following a surgical repair. However, future studies are needed to determine the clinical usefulness of these engineered strategies. Cite this article: Bone Joint J 2020;102-B(8):1095-1106.

Composition and characteristics of trabecular bone in osteoporosis and osteoarthritis.

BACKGROUND: Bone strength depends on multiple factors such as bone density, architecture and composition turnover. However, the role these factors play in osteoporotic fractures is not well understood. PURPOSE: The aim of this study was to analyze trabecular bone architecture, and its crystal and organic composition in humans, by comparing samples taken from patients who had a hip fracture (HF) and individuals with hip osteoarthritis (HOA). METHODS: The study included 31 HF patients and 42 cases of HOA who underwent joint replacement surgery between 1/1/2013 and 31/12/2013. Trabecular bone samples were collected from the femoral heads and analyzed using a dual-energy X-ray absorptiometry, micro-CT, and solid-state high-resolution magic-angle-spinning nuclear magnetic resonance (MAS-NMR) spectroscopy. RESULTS: No differences in proton or phosphorus concentration were found between the two groups using 1H single pulse, 31P single pulse, 31P single pulse with proton decoupling NMR spectroscopy, in hydroxyapatite (HA) c-axis or a-axis crystal length. Bone volume fraction (BV/TV), trabecular number (Tb.N), and bone mineral density (BMD) were higher in the HO group than in the HF group [28.6% ± 10.5 vs 20.3% ± 6.6 (p = 0.026); 2.58 mm-1 ± 1.57 vs 1.5 mm-1 ± 0.79 (p = 0.005); and 0.39 g/cm2 ± 0.10 vs. 0.28 g/cm2 ± 0.05 (p = 0.002), respectively]. The trabecular separation (Tp.Sp) was lower in the HO group 0.42 mm ± 0.23 compared with the HF group 0.58 mm ± 0.27 (p = 0.036). In the HO group, BMD was correlated with BV/TV (r = 0.704, p < 0.001), BMC (r = 0.853, p < 0.001), Tb.N (r = 0.653, p < 0.001), Tb.Sp (-0.561, p < 0.001) and 1H concentration (-0.580, p < 0.001) in the HO group. BMD was not correlated with BV/TV, Tb.Sp, Tb.Th, Tb.N, Tb.PF, 1H concentration or HA crystal size in the HF group. CONCLUSIONS: Patients with HO who did not sustain previous hip fractures had a higher femoral head BMD, BV/TV, and Tb.N than HF patients. In HO patients, BMD was positively correlated with the BV/TV and Tb.N and negatively correlated with the femoral head organic content and trabecular separation. Interestingly, these correlations were not found in HF patients with relatively lower bone densities. Therefore, osteoporotic patients with similar low bone densities could have significant microstructural differences. No differences were found between the two groups at a HA crystal level.

Altered topological blueprint of trabecular bone associates with skeletal pathology in humans.

Bone is a hierarchically organized biological material, and its strength is usually attributed to overt factors such as mass, density, and composition. Here we investigate a covert factor - the topological blueprint, or the network organization pattern of trabecular bone. This generally conserved metric of an edge-and-node simplified presentation of trabecular bone relates to the average coordination/valence of nodes and the equiangular 3D offset of trabeculae emanating from these nodes. We compare the topological blueprint of trabecular bone in presumably normal, fractured osteoporotic, and osteoarthritic samples (all from human femoral head, cross-sectional study). We show that bone topology is altered similarly in both fragility fracture and in joint degeneration. Decoupled from the morphological descriptors, the topological blueprint subjected to simulated loading associates with an abnormal distribution of strain, local stress concentrations and lower resistance to the standardized load in pathological samples, in comparison with normal samples. These topological effects show no correlation with classic morphological descriptors of trabecular bone. The negative effect of the altered topological blueprint may, or may not, be partly compensated for by the morphological parameters. Thus, naturally occurring optimization of trabecular topology, or a lack thereof in skeletal disease, might be an additional, previously unaccounted for, contributor to the biomechanical performance of bone, and might be considered as a factor in the life-long pathophysiological trajectory of common bone ailments.

Patient survival and surgical re-intervention predictors for intracapsular hip fractures.

BACKGROUND: Choosing between total hip replacement (THR) and partial hip replacement (PHR) for patients with intracapsular hip fractures is often based on subjective factors. Predicting the survival of these patients and risk of surgical re-intervention is essential to select the most adequate implant. METHODS: We conducted a retrospective cohort study on mortality of patients over 70 years with intracapsular hip fractures who were treated between January 2010 and December 2013, with either PHR or THR. Patients' information was withdrawn from our local computerized database. The age-adjusted Charlson comorbidity index (ACCI) and American Society of Anesthesiologists (ASA) score were calculated for all patients. The patients were followed for 2 years after surgery. Survival and surgical re-intervention rates were compared between the two groups using a Multivariate Cox proportional hazard model. RESULTS: A total of 356 individuals were included in this study. At 2 years of follow-up, 221 (74.4%) of the patients with ACCI score≤7 were still alive, in contrast to only 20 (29.0%) of those with ACCI score>7. In addition, 201 (76.2%) of the patients with ASA score≤3 were still alive after 2 years, compared to 30 (32.6%) of individuals with ASA >3. Patients with the ACCI score>7, and ASA score>3 had a significant increase in all-cause 2-year mortality (adjusted hazard ratio of 3.2, 95% CI 2.2-4.6; and 3.12, 95% CI 2.2-4.5, respectively). Patients with an ASA score>3 had a quasi-significant increase in the re-intervention risk (adjusted hazard ratio 2.2, 95% CI 1.0-5.1). The sensitivity, specificity, positive predictive value and negative predictive values of ACCI in predicting 2-year mortality were 39.2%, 91.1%, 71%, and 74.4%, respectively. On the other hand, the sensitivity, specificity, positive predictive value and negative predictive values of ASA score in predicting 2-year mortality were 49.6%, 79.1%, 67.4%, and 76.1%, respectively. CONCLUSIONS: Both ACCI and ASA scales were able to predict the 2-year survival of patients with intracapsular hip fractures. The ASA scale was also able to predict the risk of re-intervention in these patients.

Blisters in Ankle Fractures: A Retrospective Cohort Study.

The most frequent postoperative complications after an ankle fracture are usually skin related. We present the results of a retrospective study of 112 patients with ankle fracture who had undergone open reduction and internal fixation from January 2014 to December 2014. The following features were analyzed: patient comorbidities, fracture type, the presence of an open fracture or fracture-dislocation, timing and duration of surgery, preoperative glucose level, and short-term complications (i.e., blisters, wound dehiscence, deep and superficial infections, and reintervention). The mean age of the patients was 50.38 years. Fracture blisters were present in 20.5% of the cases. The operative time was 75.74 ± 25.09 minutes for patients with blisters and 64.48 ± 19.73 minutes for patients without blisters (p = .023). The preoperative blood glucose levels were 122.96 ± 28.46 g/dL in the patients with blisters and 106.70 ± 21.32 g/dL in the patients without blisters (p = .003). No statistically significant differences were observed between the patients who had undergone surgery <24 hours after injury and those who had done so >24 hours after injury. In conclusion, the presence of postoperative blisters in patients with ankle fractures was associated with prolonged surgical procedures and high serum glucose levels.