Diabetic Rats Induced Using a High-Fat Diet and Low-Dose Streptozotocin Treatment Exhibit Gut Microbiota Dysbiosis and Osteoporotic Bone Pathologies.

Type 2 diabetes mellitus (T2DM) presents a challenge for individuals today, affecting their health and life quality. Besides its known complications, T2DM has been found to contribute to bone/mineral abnormalities, thereby increasing the vulnerability to bone fragility/fractures. However, there is still a need for appropriate diagnostic approaches and targeted medications to address T2DM-associated bone diseases. This study aims to investigate the relationship between changes in gut microbiota, T2DM, and osteoporosis. To explore this, a T2DM rat model was induced by combining a high-fat diet and low-dose streptozotocin treatment. Our findings reveal that T2DM rats have lower bone mass and reduced levels of bone turnover markers compared to control rats. We also observe significant alterations in gut microbiota in T2DM rats, characterized by a higher relative abundance of Firmicutes (F) and Proteobacteria (P), but a lower relative abundance of Bacteroidetes (B) at the phylum level. Further analysis indicates a correlation between the F/B ratio and bone turnover levels, as well as between the B/P ratio and HbA1c levels. Additionally, at the genus level, we observe an inverse correlation in the relative abundance of Lachnospiraceae. These findings show promise for the development of new strategies to diagnose and treat T2DM-associated bone diseases.

Crosslinking chitosan with glucose via the modified Maillard reaction promotes the osteoinduction of mouse MC3T3-E1 pre-osteoblasts.

Bone defects are a common clinical issue, but therapeutic efficiency can be challenging in cases of more considerable traumas or elderly patients with degenerated physiological metabolism. To address this issue, a more suitable cell-biomaterial construct promoting bone regeneration has been extensively investigated, with the chitosan scaffold being considered a potential candidate. In this study, chitosan was crosslinked with different doses of glucose (CTS-10~50%Glc) using a modified Maillard reaction condition to develop a more appropriate cell-biomaterial construct. Mouse MC3T3-E1 pre-osteoblasts were seeded onto the scaffolds to examine their osteoinductive capability. The results showed that CTS-Glc scaffolds with higher glucose contents effectively improved the adhesion and survival of mouse MC3T3-E1 pre-osteoblasts and promoted their differentiation and mineralization. It was further demonstrated that the membrane integrin α5 subunit of pre-osteoblasts is the primary adhesion molecule that communicates with CTS-Glc scaffolds. After that, Akt signaling was activated, and then bone morphogenetic protein 4 was secreted to initiate the osteoinduction of pre-osteoblasts. The prepared CTS-Glc scaffold, with enhanced osteoinduction capability and detailed mechanism elucidations, offers a promising candidate material for advancing bone tissue engineering and clinical regenerative medicine. As a result, this study presents a potential tool for future clinical treatment of bone defects.

Comparison of Surgical Outcomes and Predictors in Patients with Monomicrobial Necrotizing Fasciitis and Sepsis Caused by Vibrio vulnificus, Aeromonas hydrophila, and Aeromonas sobria.

Background: Monomicrobial necrotizing fasciitis caused by Vibrio vulnificus, Aeromonas hydrophila, and Aeromonas sobria are often associated with high mortality rates. The purpose of this study was to compare the independent predictors related to outcomes between Vibrio vulnificus and Aeromonas species necrotizing fasciitis. Patients and Methods: Monomicrobial necrotizing fasciitis caused by Vibrio vulnificus (60 patients) and Aeromonas species (31 patients) over an 11-year period were reviewed retrospectively. Differences in mortality, patient characteristics, clinical presentations, and laboratory data were compared between the Vibrio vulnificus and Aeromonas species groups, and between the death and the survival subgroups of patients with Aeromonas species. Results: Six patients in the Vibrio vulnificus group (10%) and 11 in the Aeromonas species group (32.3%) died. Fifty-nine patents had bacteremia and 16 patients died (27.1%). Patients who had Vibrio vulnificus had a higher incidence of bacteremia. The patients who had Aeromonas species presenting with bacteremia were significantly associated with death. The death subgroup of patients with Aeromonas necrotizing fasciitis had a higher incidence of bacteremia, higher counts of banded leukocytes, lower platelet counts, lower total lymphocyte counts, and lower serum albumin level than the survival subgroup. Conclusions: Monomicrobial necrotizing fasciitis caused by Aeromonas species was characterized by more fulminating and higher mortality than that of Vibrio vulnificus, even after early fasciotomy and third-generation cephalosporin antibiotic therapy. Those risk factors, such as bacteremia, shock, lower platelet counts, lower albumin levels, and antibiotic resistance were associated with mortality, which should alert clinicians to pay more attention to and aggressively treat those patients with Aeromonas and Vibrio necrotizing fasciitis.

Silver-Catalyzed Carbon Dioxide Fixation on Alkynylindenes.

The synthesis of polycyclic indene derivatives via silver-catalyzed carbon dioxide fixation on 2-alkynylindene derivatives was achieved by nucleophilic addition of the indenyl anion to carbon dioxide involving carbon-carbon bond formation and subsequent intramolecular cyclization to the alkyne part activated by a silver catalyst. This cascade process could be applied to various substrates to obtain the corresponding products in high yields. The endo/exo selectivity of the cyclization could be controlled by the steric or electronic effect of the substituents on the substrates, and 6-endo-selective cyclization was realized to afford α-pyrone-fused indenes.

Stearoyl-CoA Desaturase-1 Attenuates the High Shear Force Damage Effect on Human MG63 Osteosarcoma Cells.

Mechanical regulation is known as an important regulator in cancer progression and malignancy. High shear force has been found to inhibit the cell cycle progression and result in cell death in various cancer cells. Stearoyl-CoA desaturase (SCD)-1, one of the important lipogenic enzymes, has recently been indicated as a potential pharmaceutical target in cancer therapy. In this study, we determined whether the cell fate control of shear force stimulation is through regulating the SCD-1 expression in cancer cells. Human MG63 osteosarcoma cells were used in this study. 2 and 20 dynes/cm2 shear forces were defined as low and high intensities, respectively. A SCD-1 upregulation in human MG63 osteosarcoma cells under 20, but not 2, dynes/cm2 shear force stimulation was shown, and this induction was regulated by Smad1/5 and peroxisome proliferator-activated receptor δ (PPARδ) signaling. Moreover, gene knockdown of PPARδ and SCD-1 in human MG63 osteosarcoma cells attenuated the differentiation inhibition and resulted in much more cell death of high shear force initiation. The present study finds a possible auto-protective role of SCD-1 upregulation in high shear force-damaged human MG63 osteosarcoma cells. However, its detailed regulation in the cancer fate decision of high shear force should be further examined.

Hepatic disease and the risk of mortality of Vibrio vulnificus necrotizing skin and soft tissue infections: A systematic review and meta-analysis.

BACKGROUND: Vibrio vulnificus necrotizing skin and soft tissue infections (VNSSTIs) are associated with a high mortality rate that varies remarkably with host susceptibility. Hepatic disease (HD) is considered the key risk factor for high VNSSTIs incidence and mortality; however, there is limited evidence in the literature to support this observation. METHODOLOGY: We examined all reported cases of VNSSTIs and associated mortality rates between 1966 and mid-2018. The PubMed, Medline and Cochrane Library databases were systematically searched for observational studies on patients with VNSSTIs. Twelve studies with 1157 total patients with VNSSTIs were included in the analysis. From the pooled dataset, nearly half (46.8%) of the patients with VNSSTIs had HD. The mortality rate in HD patients with VNSSTIs was 53.9% (n = 292/542), which was considerably higher than the mortality rate of 16.1% (n = 99/615) in non-HD patients. Patients with HD contracted VNSSTIs were found to be two or more times (RR = 2.61, 95% CI = 2.14-3.19) as likely to die compared with those without HD. Besides, liver cirrhosis (LC), the end-stage HD, was confirmed to be a significant risk factor, with risk ratios of 1.84 (95% CI 1.21-2.79) and 2.00 (95% CI 1.41-2.85) when compared to non-LC and non-HD, respectively. CONCLUSIONS: HD with or without LC can be associated with infections and complications from V. vulnificus. Clinicians should aggressively approach care and management of acutely and/or critically ill patients with VNSSTIs.

Hyperglycemia inhibits osteoblastogenesis of rat bone marrow stromal cells via activation of the Notch2 signaling pathway.

Background: Bone fragility and related fractures are increasingly being recognized as an important diabetic complication. Mesenchymal progenitors often serve as an important source of bone formation and regeneration. In the present study, we have evaluated the effects of diabetes on osteoblastogenesis of mesenchymal progenitors. Methods: Primary bone marrow stromal cells (BMSCs) were isolated from control and streptozotocin-induced diabetic rats. These cells were evaluated for the effects of in vivo hyperglycemia on the survival and function of mesenchymal progenitors. We concomitantly investigated the effects of different concentrations of glucose, osmolality, and advanced glycation end product (AGE) on osteogenic differentiation and matrix mineralization of rat bone marrow mesenchymal stem cells (RMSC-bm). The relationship between the expression levels of Notch proteins and the corresponding ALP levels was also examined. Results: Our results revealed that in vivo hyperglycemia increased cell proliferation rate but decreased osteogenic differentiation and matrix mineralization of primary rat BMSCs. In vitro high glucose treatment, instead of high AGE treatment, induced a dose-dependent inhibition of osteoblastogenesis of RMSC-bm cells. Activation of the Notch2 signaling pathway, instead of the Notch1 or osmotic response pathways, was associated with these diabetic effects on osteoblastogenesis of mesenchymal progenitors. Conclusions: Hyperglycemia might inhibit osteoblastogenesis of mesenchymal progenitors via activation of the Notch2 signaling pathway.

Zoledronate induces cell cycle arrest and differentiation by upregulating p21 in mouse MC3T3-E1 preosteoblasts.

Background: Increasing research has recently been focused on the supplementary use of drugs such as bisphosphonates that are known to influence bone turnover to prevent and treat periprosthetic bone loss and subsequent implant loosening following total joint replacements. However, there are still concerns about the conflicting effects of bisphosphonate treatment on osteoblastic bone formation in the literature. Methods: In this study, we investigate the role of zoledronate (ZOL) in regulating cell cycle distribution and differentiation in mouse MC3T3-E1 preosteoblasts and also explore the mechanism underlying this effect of ZOL. We examined the expression levels of osteocalcin (OCN) by quantitative polymerase chain reaction (qPCR), the total amount of CDK6, p21 and p27 proteins by Western blot analysis, and the cell cycle distribution by flow cytometric analysis in mouse MC3T3-E1 preosteoblasts to evaluate the effect of ZOL. Small interfering RNAs (siRNAs) were used to assess the individual contributions of genes to specific osteoblast phenotypes. Results: In addition to increased OCN expression, we found that ZOL treatment induces the G0/G1 arrest and results in the increase of p21 and p27 expressions and decrease of CDK6 expression in mouse MC3T3-E1 preosteoblasts. Both p21 and p27 mediates ZOL-induced cell cycle exit; however, p21, but not p27, is responsible for the increase of ZOL-induced OCN expression in these cells. Conclusions: These results endorse that ZOL might have an anabolic effect on osteoblasts. The CDK inhibitor p21 plays a key role in regulating osteoblast differentiation by controlling proliferation-related events in mouse MC3T3-E1 preosteoblasts.

The outcome of surgical management of proximal humeral fractures using locking plates: comparison between locking plates with different geometry.

BACKGROUND: Locking plate fixation appears to be a standard treatment for proximal humeral fracture. Different locking plate designs might result in different radiographic and functional outcomes. The original version of the Proximal Humeral Internal Locking System (PHILOS; DePuy Synthes, Warsaw, IN, USA) occupied the largest volume of the humeral head by screw distribution, whereas the Zimmer Periarticular Locking Plate (ZPLP) system (Zimmer Biomet, Warsaw, IN, USA) occupied the smallest. METHODS: We enrolled 50 patients undergoing ZPLP treatment and 50 undergoing PHILOS treatment. RESULTS: The postoperative amount of impaction was significantly higher using the ZPLP System than using the PHILOS. Subgroup analysis showed that medial calcar support was another critical factor that affected surgical outcomes, especially when using the ZPLP System. CONCLUSION: The amount of postoperative impaction was significantly higher when the ZPLP was used compared with the PHILOS locking plate. Medial calcar support is another critical factor that affects surgical outcomes. However, no significant differences in functional outcomes (Constant-Murley score) between the ZPLP System and the PHILOS were noted at the 12-month follow-up.

Pseudoaneurysm rupture with hemorrhagic shock in a patient with periprosthetic hip joint infection: A case report.

RATIONALE: Although pseudoaneurysm (PA) formation following primary and revision total hip arthroplasty (THA) is rare, PA rupture may lead to severe complications that can result in a threat to life and limb. PATIENT CONCERNS: A 65-year-old man presented with acute hemorrhagic discharge for one day from the chronic hip sinus secondary to revision THA that had been performed 6 years ago, for which he had received multiple courses of debridement, antibiotics, and implant retention procedures owing to periprosthetic joint infection (PJI). DIAGNOSES: Radiographs showed septic loosening of both the femoral and acetabular components, with medial migration of the component beyond Kohler's line. Contrast-enhanced computed tomography angiogram of the abdomen and pelvis of the patient demonstrated a large PA of the right external iliac artery (EIA), measuring 6.1 cm × 7.7 cm in diameter and 9.1 cm in length. INTERVENTIONS: A ball-shaped antibiotic-loaded cement spacer (ALCS) was used to tamponade a bleeding PA, treat the coexisting PJI, and thus facilitate endovascular stent-graft repair (ESGR) later on. OUTCOMES: The ESGR resulted in complete exclusion of the PA and successfully controlled the bleeding. The patient underwent a successful revision THA 6 months after stent insertion. Neither stent-graft infection nor recurrent PJI were detected at 18 months. LESSONS: Given the potential of a PA for causing significant morbidity and mortality, the surgeon should have an elevated index of suspicion in the presence of intrapelvic migration of the acetabular component. While facing a PA rupture with/without hemorrhagic shock in patients with coexisting hip PJI, ALCS ball implantation and subsequent ESGR might be an effective method to save the patient's life and limb.

Treatment of displaced transverse fractures of the patella: modified tension band wiring technique with or without augmented circumferential cerclage wire fixation.

BACKGROUND: Displaced transverse fractures of the body of the patella are usually associated with disruption of extensor mechanism and should be fixed surgically. The most common method is a tension band wiring (TBW) technique. Some surgeons concurrently employ an augmented circumferential cerclage wiring (ACCW) technique to help fracture stabilization and aid in fracture healing; however, its role and effect on the treatment outcomes is unclear. METHODS: We performed a STROBE-compliant retrospective observational cohort study on all cases of acute closed patella fracture that were treated at our institution between 2006 and 2012. Of 185 episodes, 72 (38.9%) were eligible for this study according to our inclusion/exclusion criteria. We classified these subjects with AO/OTA type 34-C1.1 or 34-C2 lesions into two groups for analyses: fractures treated with modified TBW and ACCW (group 1, n = 27) and those treated with modified TBW alone (group 2, n = 45). Plain radiographs were used to evaluate radiographic outcomes and the effect of potential risk factors on fixation failure was analyzed by subgroup comparisons. RESULTS: Our results revealed that there were no significant differences in the rates of fixation failure (P = 0.620), nonunion (P = 0.620), and revision surgery (P = 0.620) between the groups. Although not statistically significant, there was a trend towards a positive risk association between fixation failure and age distribution > 60 years (10.0% vs. 0.0%, P = 0.124; OR = 8.0, P = 0.168) and > 70 years (9.4% vs. 2.5%, P = 0.321; OR = 4.0, P = 0.237) and the superficial level of the K-wires (12.0% vs. 1.5%, P = 0.117; OR = 6.3, P = 0.121). Regarding those modified TBW patients concurrently treated with an ACCW, the potential risk association between fixation failure and the superficial level of the K-wire was prone to increase further (28.6% vs. 0.0%, P = 0.060; OR = 18.6, P = 0.071). CONCLUSIONS: Concurrent application of an ACCW might be needless and not efficacious to help fracture stabilization and healing in patients having been treated with modified TBW for displaced transverse fractures of the body of the patella. Adherence to correct surgical technique such as putting the K-wires at the proper level and securing control of the both ends of the K-wires may be more important and help in improving outcomes.

Total knee arthroplasty in patients with Ranawat type-II valgus arthritic knee with a marked coronal femoral bowing deformity: comparison between computer-assisted surgery and intra-articular resection.

BACKGROUND: Proper limb and component alignments as well as soft tissue balance are vital for the longevity and optimal long-term outcomes of total knee arthroplasty (TKA). This procedure is technically demanding in patients with Ranawat type-II valgus arthritic knees with marked coronal femoral bowing. Computer-assisted surgery (CAS) and intra-articular bone resection with TKA are the treatments of choice for patients with ipsilateral extra-articular deformity. In theory, both CAS and intra-articular bone resection are beneficial in Ranawat type-II valgus arthritic knees with marked coronal femoral bowing deformity, but the literature on this topic is sparse. We compared the benefits of using these two techniques for TKA under this circumstance. METHODS: Patients who had Ranawat type-II valgus arthritic knees and marked coronal femoral bowing deformity and had undergone TKA at our hospital between 2005 and 2013 were enrolled in this retrospective study. Patients treated with CAS were assigned to the CAS-TKA group; patients treated with intra-articular bone resection were assigned to the Bone-Resect-TKA group. Radiographic parameters and clinical outcomes (International Knee Society (IKS) scores and patellar scores) in both groups were compared. RESULTS: Forty-seven patients (50 knees) met the inclusion criteria: 22 knees in the CAS-TKA group and 28 knees in the Bone-Resect-TKA group. Lateral retinaculum release was significantly (P = 0.008) higher in the Bone-Resect-TKA group. The joint-line was significantly properly restored in the CAS-TKA group (P = 0.011). The reconstructed mechanical axis was significantly (P = 0.012) closer to normal in the CAS-TKA group than in the Bone-Resect-TKA group. For component alignment, the femoral valgus and femoral flexion angles were significantly better in the CAS-TKA group (P = 0.002 and P = 0.006, respectively), but not the tibial valgus, tibial flexion, or patellar tilting angles. IKS scores and patellar scores were not significantly different between groups at a mean follow-up of 60.2 months. CONCLUSIONS: CAS-TKA was effective for obtaining proper alignment and joint-line restoration in patients with Ranawat type-II valgus arthritic knees and marked coronal femoral bowing deformity, but not for yielding better clinical outcomes. Additional large-scale prospective randomized cohort studies with long-term follow-ups are necessary to make evidence-based recommendations.

Effects of teriparatide on cementless bipolar hemiarthroplasty in patients with osteoporotic femoral neck fractures.

BACKGROUND: For osteoporotic femoral neck fractures, suitable bone-implant stability is critical for pain relief, early return to daily activities and reduction of complications. Teriparatide (parathyroid hormone [PTH1-34]) can improve bone-implant stability in some basic studies. However it's use in osteoporotic femoral neck fractures treated by cementless hemiarthroplasties for the beneficial effects on bone-implant stability is sparse in the literature. The aim of this study was to determine if post-operative teriparatide administration can reduce femoral stem migration and improve early functional recovery and health-related quality of life (HRQoL). METHODS: Between 2010 and 2014, patients with osteoporotic femoral neck fracture who underwent cementless bipolar hemiarthroplasty were included into this retrospective cohort study. Group A included patients treated with cementless bipolar hemiarthroplasty only; Group B patients had additional teriparatide. Demographic data, complications, radiographic and functional outcomes as well as health-related quality of life (HRQoL) were compared. RESULTS: There were 52 hips in group A (no teriparatide) and 40 hips in group B (patient who received teriparatide). The subsidence of the femoral stem tended to be significantly decreased in the teriparatide group at 6 and 12 weeks post-operatively (p = 0.003 and p = 0.008, respectively). The Harris Hip Score (HHS) increased significantly from pre-operation to 6 weeks post-operatively and thereafter up to one year in both groups. However, there were no significant differences in terms of subsequent fracture, mortality, HHS, and HRQoL between two groups during the entire study period. CONCLUSIONS: Teriparatide significantly reduces the subsidence of the cementless femoral stem in elderly patients in the early post-operative period, but this benefit does not reflect better functional outcomes and HRQoL. Further prospective randomized large-scale cohort study is warranted for evidence-based recommendations.

The outcome of unstable proximal femoral fracture treated with reverse LISS plates.

BACKGROUND: The Russel-Taylor type 2B fractures compromised the trochanteric region and medial buttress of proximal femur. This fracture pattern limits the choice of implants and raises the risk of adverse outcomes. We aimed to (i) determine the outcome of Russel-Taylor type 2B fractures treated using reverse less invasive stabilization system plates (LISS-DF) and to (ii) learn what factors affected outcomes after osteosynthesis with reverse LISS plates. DESIGN: A retrospective study SETTING: The study was conducted at a Level III trauma center in Taiwan. METHODS: Twenty-five consecutive patients presenting with a Russel-Taylor type 2B fracture were enrolled. All cases were treated with reverse LISS plates. A Modified Radiographic Union Scale for Femur (RUSF), Radiographic parameters, functional scores, and complications were assessed. RESULTS: Union occurred in 21 cases at an average of 18.8 weeks. The average immediate postoperative neck-shaft angle was 130° (range: 122-135°) compared with 139° (range: 135-141°, p=0.05) on the contralateral side. Two cases had complications of proximal screws cutting out and two cases had broken implants. Finally, all 4 cases required repeated surgeries (16%). Malunion occurred in 4 patients and early mechanical failure (proximal screws cut out) occurred in 2. There was a significant difference in the purchase index of the proximal screws between cases with redisplacement and those without (26.4mm and 98.6mm, p=0.01). CONCLUSIONS: The use of reverse LISS plate appeared to be an alternative procedure for the specific pattern in the present study. We recommend using this reverse locking plate to treat unstable proximal femoral fractures with meticulous techniques of placing plates. Adequate purchase of the proximal locking screws might decrease the risks of complications.

Teriparatide Improves Fracture Healing and Early Functional Recovery in Treatment of Osteoporotic Intertrochanteric Fractures.

Osteoporotic intertrochanteric fractures result in serious health problems and decrease health-related quality of life (HRQoL). Faster time-to-union is important for early return to daily activities and reduction of complications. Teriparatide has been shown to accelerate fracture healing, but the literature is sparse on this topic. The aim of this study is to assess whether teriparatide accelerates fracture healing.Between 2008 and 2014, patients with osteoporotic intertrochanteric fractures who underwent surgical interventions were enrolled in this retrospective cohort study. Group 1 included patients who were not on any osteoporosis medication prior to fracture and who postoperatively received only calcium and vitamin D; patients in Group 2 were not on any osteoporosis medication prior to fracture, and received teriparatide and calcium and vitamin D postoperatively. Patients in Group 3 were those who were on alendronate prior to fracture and postfracture received teriparatide as well as calcium and vitamin D. Demographics, time-to-union, HRQoL (short-form health survey [SF]-12 physical component summary [PCS] and SF-12 mental component summary [MCS]), morbidities, mortalities, and radiographic and functional outcomes between groups were compared.A total of 189 patients were enrolled in this study. There were 83 patients in Group 1, 47 patients in Group 2, and 59 patients in Group 3. A significantly shorter time-to-union was found in the teriparatide-treated groups (mean, 13.6, 12.3, and 10.6 weeks, respectively [P = 0.002]). With regard to SF-12 PCS, the scores were significantly better in teriparatide-treated groups at 3 months (mean, 19, 28, and 29, respectively [P = 0.002]) and 6 months (mean, 28, 37, and 38, respectively [P = 0.008]). Similar inter-group differences were noted when comparing the pain scores, the ability to get around the house, the ability to get out of the house, and the ability to go shopping at 3 and 6 months. Complications and mortality were also markedly reduced in the teriparatide-treated groups.Postoperative use of teriparatide for 6 months appears to be an effective adjunct therapy in the treatment of patients with osteoporotic intertrochanteric fractures. However, because of the limited power of the study, a prospective, randomized, large-scale cohort study is still required for determining the efficacy of teriparatide.

Non-steroidal anti-inflammatory drugs and the risk of a second hip fracture: a propensity-score matching study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for elderly patients, particularly after a hip fracture. However, we are not clear about the effect of NSAIDs on the risk of a second hip fracture because of confounding factors. METHODS: This was a Taiwan National Health Insurance Research Database-based study using propensity-score matching (PSM) to control for confounding. Enrollees were selected from patients with a hip fracture during 1996-2004 and followed longitudinally until December 2009. After PSM for comorbidities and bisphosphonate therapy, 94 patients with a second hip fracture were assigned to the Cases group and 461 without it to the Controls group. The target drugs are NSAIDs; paracetamol and dexamethasone are used for comparison. RESULTS: The correlation between the mean daily-dose (MDD) ratios of NSAIDs and the probability values of the current statistical tests were highly negative (Pearson's r = -0.920, P = 0.003), which indicated that the higher the MDD ratios, the greater the risks of a second hip fracture. A Kaplan-Meier survival analysis showed a time-dependent trend of increasing risk of a second hip fracture in patients taking NSAIDs (P < 0.001). Moreover, patients ≥ 60 years old had a higher risk of a second hip fracture than did those <60 and taking the NSAIDs diclofenac (P = 0.016) and celecoxib (P = 0.003) and the corticosteroid dexamethasone (P = 0.018), but not those taking analgesic paracetamol (P = 0.074). CONCLUSIONS: We conclude that taking NSAIDs after a fragility hip fracture dose- and time-dependently significantly increases the risk of a second hip fracture, especially in elderly patients. To lower the risk of a second hip fracture, any underlying causes for excessively using NSAIDs should be treated and thus fewer NSAIDs prescribed after a first hip fracture.

The effects of zoledronate on the survival and function of human osteoblast-like cells.

BACKGROUND: Prolonged bisphosphonate treatment might suppress bone remodeling to the extent that normal bone repair is impaired. While this adverse side effect is usually ascribed to the negative effects of bisphosphonates on osteoclast survival and function, these effects on osteoblasts are still unclear. METHODS: In the current study, we hypothesized that zoledronate (ZOL) at the µM level might present negative effects on osteoblast survival and function. In vitro analyses of proliferation, migration and differentiation were performed on human osteoblast-like cells. RESULTS: Our results revealed that ZOL treatment dose- and time-dependently induced apoptosis of osteoblasts after concentrations had reached 10 µM (p < 0.001). The concentrations at which ZOL inhibited osteoblast migration by 50 % were between 10 and 15 µM. Moreover, there was a dose-dependent reduction in the extent of matrix mineralization, but without a concomitant inhibition of osteogenic differentiation in terms of secreted type I collagen and osteocalcin and of alkaline phosphatase activity per viable cell. Analyses of the expression of osteogenic genes confirmed that ZOL at the µM level had no effects on osteogenic differentiation of osteoblasts. CONCLUSION: We concluded that ZOL at the µM level affected osteoblast survival and migration, but did not affect differentiation. The pathophysiological implications of ZOL at the µM level on skeletal disorders need to be investigated and clarified in the future researches.

The Effects of Dorsal Cortical Comminution on Radiographic Results following Percutaneous Pinning for Extra-Articular Colles' Fracture.

A number of studies have demonstrated that dorsal cortical comminution (DCC) can predict redisplacement after nonoperative treatment of Colles' fractures; however, the effects of a DCC defect on radiographic outcomes following percutaneous pinning for dorsally displaced extraarticular Colles' fractures are unclear. We, therefore, performed a retrospective study on 85 patients who sustained such fractures treated with percutaneous pinning within 2006-2009. The main outcome measures included four radiographic parameters, including radial height, radial inclination, radial tilt, and ulnar variance. The radiological results showed that all fractures after percutaneous pinning followed the same time series changes and patterns of fracture collapse regardless of the presence of a DCC defect. The use of the pinning construct is to provide support for static loading but not for dynamic loading. Although the final radiographic outcomes were classified as acceptable in fractures with and without DCC, we recommend that a different approach in the management of displaced Colles' fractures might be necessary in consideration of increasing patient expectations of health care.