Effects of the duration of transcutaneous CO2 application on the facilitatory effect in rat fracture repair.

BACKGROUND: Carbon dioxide therapy has been reported to be effective in treating certain cardiac diseases and skin problems. Although a previous study suggested that transcutaneous carbon dioxide application accelerated fracture repair in association with promotion of angiogenesis, blood flow, and endochondral ossification, the influence of the duration of carbon dioxide application on fracture repair is unknown. The aim of this study was to investigate the effect of the duration of transcutaneous carbon dioxide application on rat fracture repair. METHODS: A closed femoral shaft fracture was created in each rat. Animals were randomly divided into four groups: the control group; 1w-CO2 group, postoperative carbon dioxide treatment for 1 week; 2w-CO2 group, postoperative carbon dioxide treatment for 2 weeks; 3w-CO2 group, postoperative carbon dioxide treatment for 3 weeks. Transcutaneous carbon dioxide application was performed five times a week in the carbon dioxide groups. Sham treatment, where the carbon dioxide was replaced with air, was performed for the control group. Radiographic, histological, and biomechanical assessments were performed at 3 weeks after fracture. RESULTS: The fracture union rate was significantly higher in the 3w-CO2 group than in the control group (p < 0.05). Histological assessment revealed promotion of endochondral ossification in the 3w-CO2 group than in the control group. In the biomechanical assessment, all evaluation items related to bone strength were significantly higher in the 3w-CO2 group than in the control group (p < 0.05). CONCLUSIONS: The present study, conducted using an animal model, demonstrated that continuous carbon dioxide application throughout the process of fracture repair was effective in enhancing fracture healing.

Topical cutaneous application of carbon dioxide via a hydrogel for improved fracture repair: results of phase I clinical safety trial.

BACKGROUND: Clinicians have very limited options to improve fracture repair. Therefore, it is critical to develop a new clinically available therapeutic option to assist fracture repair biologically. We previously reported that the topical cutaneous application of carbon dioxide (CO2) via a CO2 absorption-enhancing hydrogel accelerates fracture repair in rats by increasing blood flow and angiogenesis and promoting endochondral ossification. The aim of this study was to assess the safety and efficacy of CO2 therapy in patients with fractures. METHODS: Patients with fractures of the femur and tibia were prospectively enrolled into this study with ethical approval and informed consent. The CO2 absorption-enhancing hydrogel was applied to the fractured lower limbs of patients, and then 100% CO2 was administered daily into a sealed space for 20 min over 4 weeks postoperatively. Safety was assessed based on vital signs, blood parameters, adverse events, and arterial and expired gas analyses. As the efficacy outcome, blood flow at the level of the fracture site and at a site 5 cm from the fracture in the affected limb was measured using a laser Doppler blood flow meter. RESULTS: Nineteen patients were subjected to complete analysis. No adverse events were observed. Arterial and expired gas analyses revealed no adverse systemic effects including hypercapnia. The mean ratio of blood flow 20 min after CO2 therapy compared with the pre-treatment level increased by approximately 2-fold in a time-dependent manner. CONCLUSIONS: The findings of the present study revealed that CO2 therapy is safe to apply to human patients and that it can enhance blood flow in the fractured limbs. TRIAL REGISTRATION: This study has been registered in the UMIN Clinical Trials Registry (Registration number: UMIN000013641, Date of registration: July 1, 2014).

Escherichia coli-derived BMP-2-absorbed ß-TCP granules induce bone regeneration in rabbit critical-sized femoral segmental defects.

PURPOSE: This study investigated whether Escherichia coli-derived bone morphogenetic protein (BMP)-2 (E-BMP-2) adsorbed onto ß-tricalcium phosphate (ß-TCP) granules can induce bone regeneration in critical-size femoral segmental defects in rabbits. METHODS: Bone defects 20 mm in size and stabilized with an external fixator were created in the femur of New Zealand white rabbits, which were divided into BMP-2 and control groups. E-BMP-2-loaded ß-TCP granules were implanted into defects of the BMP-2 group, whereas defects in the controls were implanted with ß-TCP granules alone. At 12 and 24 weeks after surgery, radiographs were obtained of the femurs and histological and biomechanical assessments of the defect area were performed. Bone regeneration was quantified using micro-computed tomography at 24 weeks. RESULTS: Radiographic and histologic analyses revealed bone regeneration in the BMP-2 group but not the control group; no fracturing of newly formed bone occurred when the external fixator was removed at 12 weeks. At 24 weeks, tissue mineral density, the ratio of bone volume to total volume, and volumetric bone mineral density of the callus were higher in the BMP-2 group than in control animals. In the former, ultimate stress, extrinsic stiffness, and failure energy measurements for the femurs were higher at 24 weeks than at 12 weeks. CONCLUSION: E-BMP-2-loaded ß-TCP granules can effectively promote bone regeneration in long bone defects.

Triweekly administration of parathyroid hormone (1-34) accelerates bone healing in a rat refractory fracture model.

BACKGROUND: Some reports have shown that intermittent parathyroid hormone (PTH) (1-34) treatment for patients with delayed union or nonunion have led to successful healing. In this study, we investigated whether systemic intermittent administration of PTH (1-34) has a beneficial effect on bone healing in a rat refractory fracture model. METHODS: We created a refractory femoral fracture model in 32 rats with periosteal cauterization that leads to atrophic nonunion at 8 weeks after surgery. Half the rats received subcutaneous intermittent human PTH (1-34) injections at a dosage of 100 µg/kg, thrice a week for 8 weeks. The other half received the vehicle only. At 8 weeks after fracture, radiographic, histological and mechanical assessments were performed. RESULTS: Radiographic assessments showed that the union rate was significantly higher in the PTH group than in the control group (P < 0.05). The degree of fracture repair as scored using the Allen grading system in histological assessment was significantly greater in the PTH group than in the control group (P < 0.05). The ultimate stress and stiffness measurements were significantly greater in the PTH group than in the control group (p < 0.05). CONCLUSIONS: We demonstrated that triweekly administration of PTH (1-34) increased union rate and accelerated bone healing in a rat refractory fracture model, suggesting that systemic administration of PTH (1-34) could become a novel and useful therapy for accelerating fracture healing in patients at high risk of delayed union or nonunion.

Altered expression of SDF-1 and CXCR4 during fracture healing in diabetes mellitus.

PURPOSE: Diabetes mellitus (DM) is known to impair fracture healing. The purpose of this study was to elucidate and compare the gene expression patterns and localization of stromal cell-derived factor 1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) during fracture healing of the femur in rats with and without DM. METHODS: Closed transverse fractures were created in the femurs of rats equally divided into a DM group and control group; DM was induced by streptozotocin. At post-fracture days five, seven, 11, 14, 21 and 28, total RNA was extracted from the fracture callus and mRNA expression levels of SDF-1 and CXCR4 were measured by real-time polymerase chain reaction. Localization of SDF-1 and CXCR4 proteins at the fracture site was determined by immunohistochemistry at days 21 and 28. RESULTS: SDF-1 expression was significantly lower in the DM group than in the healthy group on days 21 and 28, and showed a significant difference between days 14 and 21 in the healthy group. There was no significant difference in CXCR4 expression levels between the healthy and DM groups at any time point. On day 21 immunoreactivity of SDF-1 and CXCR4 was detected at the fracture site of the healthy group but no immunoreactivity was observed in the DM group. On day 28, immunoreactivity of SDF-1 and CXCR4 was detected at the fracture site in both groups. CONCLUSION: Gene expression and localization of SDF-1 and CXCR4 was altered during fracture healing, which may contribute to the impaired fracture healing in DM.

Profiling microRNA expression during fracture healing.

BACKGROUND: The discovery of microRNA (miRNA) has revealed a novel type of regulatory control for gene expression. Increasing evidence suggests that miRNA regulates chondrocyte, osteoblast, and osteoclast differentiation and function, indicating miRNA as key regulators of bone formation, resorption, remodeling, and repair. We hypothesized that the functions of certain miRNAs and changes to their expression pattern may play crucial roles during the process of fracture healing. METHODS: Standard healing fractures and unhealing fractures produced by periosteal cauterization at the fracture site were created in femurs of seventy rats, with half assigned to the standard healing fracture group and half assigned to the nonunion group. At post-fracture days 3, 7, 10, 14, 21, and 28, total RNA including miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was performed with miRNA samples from each group on post-fracture day 14. For further analysis, we selected highly up-regulated five miRNAs in the standard healing fracture group from the microarray data. Real-time PCR was performed with miRNA samples at each time point above mentioned to compare the expression levels of the selected miRNAs between standard healing fractures and unhealing fractures and investigate their time-course changes. RESULTS: Microarray and real-time polymerase chain reaction (PCR) analyses on day 14 revealed that five miRNAs, miR-140-3p, miR-140-5p, miR-181a-5p, miR-181d-5p, and miR-451a, were significantly highly expressed in standard healing fractures compared with unhealing fractures. Real-time PCR analysis further revealed that in standard healing fractures, the expression of all five of these miRNAs peaked on day 14 and declined thereafter. CONCLUSION: Our results suggest that the five miRNAs identified using microarray and real-time PCR analyses may play important roles during fracture healing. These findings provide valuable information to further understand the molecular mechanism of fracture healing and may lead to the development of miRNA-based tissue engineering strategies to promote fracture healing.

Antibiotic-impregnated calcium phosphate cement as part of a comprehensive treatment for patients with established orthopaedic infection.

BACKGROUND: The treatment of established orthopaedic infection is challenging. While the main focus of treatment is wide surgical debridement, systemic and local antibiotic administration are important adjuvant therapies. Several reports have described the clinical use of antibiotic-impregnated calcium phosphate cement (CPC) to provide local antibiotic therapy for bone infections. However, these were all individual case reports, and no case series have been reported. We report a case series treated by a single surgeon using antibiotic-impregnated CPC as part of a comprehensive treatment plan in patients with established orthopaedic infection. METHODS: We enrolled 13 consecutive patients with osteomyelitis (n = 6) or infected non-union (n = 7). Implantation of antibiotic-impregnated CPC was performed to provide local antibiotic therapy as part of a comprehensive treatment plan that also included wide surgical debridement, systemic antibiotic therapy, and subsequent second-stage reconstruction surgery. We investigated the rate of successful infection eradication and systemic/local complications. The concentration of antibiotics in the surgical drainage fluids, blood, and recovered CPC (via elution into a phosphate-buffered saline bath) were measured. RESULTS: The mean follow-up period after surgery was 50.4 (range, 27-73) months. There were no cases of infection recurrence during follow-up. No systemic toxicity or local complications from the implantation of antibiotic-impregnated CPC were observed. The vancomycin concentration in the fluid from surgical drainage (n = 6) was 527.1 ± 363.9 µg/mL on postoperative day 1 and 224.5 ± 198.4 µg/mL on postoperative day 2. In patients who did not receive systemic vancomycin therapy (n = 3), the maximum serum vancomycin level was <0.8 µg/mL. In vitro vancomycin elution was observed from the CPC that was surgically retrieved (n = 2). CONCLUSIONS: Implantation of antibiotic-impregnated CPC is an option to provide local antibiotic therapy as part of a comprehensive treatment plan.

D-dimer levels to screen for venous thromboembolism in patients with fractures caused by high-energy injuries.

BACKGROUND: The clinical relevance of D-dimer levels when screening for venous thromboembolism (VTE) in elderly patients with a hip fracture has been reported but has not been fully investigated in patients with fractures caused by high-energy injuries. The purpose of this study was to evaluate the usefulness and limitations of D-dimer in such patients. METHODS: We enrolled 80 consecutive patients who underwent surgical treatment for fracture of the pelvis or lower extremity caused by high-energy injuries. None had received pharmacological prophylaxis for VTE. All patients underwent routine ultrasonography preoperatively and postoperatively (average 6.1 days after injury and 7.8 days after surgery). Contrast-enhanced computed tomography was performed routinely at the same time points for patients with a pelvic fracture or multiple fractures. D-dimer levels were compared in patients with and without VTE. Receiver operating characteristic (ROC) curve analysis was done and the appropriate D-dimer cutoff level determined for VTE screening. RESULTS: VTE was diagnosed in 34 of the 80 patients. D-dimer levels were significantly higher in patients with VTE than without it at almost all time points preoperatively and postoperatively except in patients with an isolated lower extremity fracture. ROC curve analysis suggested moderate to high accuracy for predicting VTE in patients with a pelvic fracture or multiple fractures preoperatively and postoperatively. Cutoff levels with high sensitivity and specificity for patients with a pelvic fracture or multiple fractures were set at around 7 days after the injury and surgery. CONCLUSIONS: D-dimer can be used as a VTE screening tool in patients with fractures caused by high-energy injuries. Our results suggested that D-dimer analysis to predict VTE was useful in patients with a pelvic fracture or multiple fractures. Our results also suggested that it was less useful for predicting VTE in patients with an isolated lower extremity fracture.

Comparative analysis of rat mesenchymal stem cells derived from slow and fast skeletal muscle in vitro.

PURPOSE: Skeletal muscle comprises different kinds of muscle fibres that can be classified as slow and fast fibres. The purpose of this study was to compare the yield, proliferation, and multi-potentiality of rat mesenchymal stem cells (MSCs) from the tibialis anterior (TA; fast muscle) and soleus (SO; slow muscle) in vitro. METHODS: The TA and SO muscles were harvested, and isolated cells were plated. After two hours, the cells were washed extensively to remove any cell that did not adhere to the cell culture plate. The adherent cells, namely MSCs, were then cultured. Both types of MSCs were differentiated toward the osteogenic, chondrogenic and adipogenic lineages using lineage specific induction factors. RESULTS: The colony-forming unit fibroblast (CFU-F) assay revealed that the SO contained significantly higher quantities of MSCs than the TA. The self-renewal capacity of MSCs derived from the TA was significantly higher at later passages (passage 9-11). Both types of MSCs exhibited similar cell surface antigens to bone marrow (BM)-derived MSCs and were positive for CD29, CD44, and CD90 and negative for CD11b, CD34, and CD45. TA-derived MSCs were superior in terms of osteogenic differentiation capacity, but there was no significant difference in chondrogenic and adipogenic differentiation capacity. CONCLUSION: Our results demonstrated significant differences in the properties of muscle-derived MSCs from different muscle types (i.e. fast or slow muscles). The greater expandability and osteogenic differentiation ability of TA-derived MSCs suggests that fast muscle may be a better source for generating large numbers of MSCs for bone regeneration.

Stimulation of superficial zone protein accumulation by hedgehog and Wnt signaling in surface zone bovine articular chondrocytes.

OBJECTIVE: To determine the roles of the hedgehog and Wnt signaling pathways in accumulation of superficial zone protein (SZP) in surface zone articular chondrocytes. METHODS: Explant cultures of disks of surface zone cartilage or isolated chondrocytes from the surface zone of articular cartilage of bovine stifle joints were cultured in serum-free chemically defined medium. Accumulation of SZP in the culture medium, in response to hedgehog proteins (sonic hedgehog [SHH] and Indian hedgehog [IHH]), Wnt proteins (Wnt-3a, Wnt-5a, and Wnt-11), agonists of the Wnt/ß-catenin pathway (glycogen synthase kinase 3ß [GSK-3ß] inhibitors), and antagonists of the Wnt/ß-catenin pathway, was investigated. The interaction between transforming growth factor ß1 (TGFß1) and hedgehog proteins or antagonists of the Wnt/ß-catenin pathway was also investigated. RESULTS: Hedgehog proteins stimulated SZP accumulation. Activation of the Wnt/ß-catenin pathway by Wnt-3a and GSK-3ß inhibitors led to inhibition of SZP accumulation; however, Wnt-5a and Wnt-11 had no influence on SZP accumulation. Conversely, antagonists of the Wnt/ß-catenin pathway stimulated SZP accumulation. In addition, there were combinatorial effects of TGFß1 and hedgehog proteins or antagonists of the Wnt/ß-catenin pathway on SZP accumulation. CONCLUSION: SHH and IHH signaling has a stimulatory effect on SZP accumulation in surface zone cartilage and isolated articular chondrocytes. These findings provide insight into the regulatory mechanisms of articular cartilage homeostasis and maintenance by morphogens.

No difference between double-high insert and medial-pivot insert in TKA.

PURPOSE: To compare the clinical midterm results in ADVANCE total knee arthroplasty (TKA) with double-high (DH) insert, with same type implant with medial-pivot (MP) insert. METHOD: Forty ADVANCE TKAs were randomly divided into two groups, and two different design insert, DH insert, and MP insert were used in each group. At midterm, 4-5 years after surgery, Knee Society Scores (KSS), Knee Society Functional Scores (KSFS), range of motion (ROM), and UCLA activity score were assessed and reported in this study. RESULTS: Midterm clinical results, including ROM and KSS, were comparable with both groups. KSFS and UCLA activity score were equally good between the two groups. CONCLUSION: The results in this study revealed equally good clinical results with these types of implants at midterm follow-up, although the significant better ROM has not achieved by using DH insert. We concluded that the selection of inserts only could not achieve the better clinical results, including ROM and activity level in this study. LEVEL OF EVIDENCE: Therapeutic studies-investigating the results of treatment, Level II.

Efficient derivation of osteoprogenitor cells from induced pluripotent stem cells for bone regeneration.

PURPOSE: There has been great interest in the use of induced pluripotent stem cells (iPSCs) in bone regenerative strategies. To generate osteoprogenitor cells from iPSCs, the most widely used protocol relies on an intermediate using embryoid body (EB) formation. We hypothesized that an osteoprogenitor cell population could be efficiently generated from iPSCs by employing a "direct-plating method" without the EB formation step. METHODS: Murine iPSC colonies were dissociated with trypsin-EDTA, and obtained single cells were cultured on gelatin-coated plates in MSC medium and FGF-2. Adherent homogeneous fibroblast-like cells obtained by this direct-plating technique were termed as direct-plated cells (DPCs). Expression levels of Oct-3/4 mRNA were analysed by real-time PCR. DPCs were evaluated for cell-surface protein expression using flow cytometry. After osteogenic induction, osteogenic differentiation ability of DPCs was evaluated. RESULTS: The expression level of Oct-3/4 in DPCs was significantly down-regulated compared to that observed in iPSCs, suggesting that the cells lost pluripotency. Flow cytometry analysis revealed that DPCs exhibited cell-surface antigens similar to those of bone marrow stromal cells. Furthermore, the cells proved to have a high osteogenic differentiation capacity, which was confirmed by the significant increase in alkaline phosphatase activity, the expression levels of osteogenic genes, and calcium mineralization after 14-day osteogenic induction. CONCLUSIONS: These findings indicate that our novel direct-plating method provides a clinically applicable, simple, and labour-efficient system for generating large numbers of homogeneous iPSC-derived osteoprogenitor cells for bone regeneration.

Multicenter study on atypical femoral fractures in patients with bone metastases taking bone- modifying agents.

Bone-modifying agents (BMAs), with bone-resorptive inhibitory effects, such as zoledronic acid and denosumab, are widely used at higher doses for bone-related events caused by bone metastasis of malignant tumors. These drugs have been suggested to be associated with atypical femoral fractures (AFFs), and the relationship between BMAs and AFFs has attracted attention. To investigate the clinical features including bone union time of AFFs in patients administered BMA for bone metastasis, we conducted a retrospective multicenter study. Thirty AFFs from 19 patients were enrolled in this study. Thirteen patients had bilateral AFFs, and nineteen AFFs had prodromal symptoms. Eighteen AFFs underwent surgery after complete fracture, three failed to achieve bone union and required nonunion surgery, and 11 AFFs that achieved bone union had an average period until bone union of 16.2 months, which was much longer than that previously reported for ordinary AFFs. Seven patients discontinued the BMAs, but not due to AFFs. Stopping BMAs in patients with bone metastasis would make it difficult to secure their performance of activities of daily living, and AFF with BMA administration might require a longer time for union. Therefore, it would be important to prevent incomplete AFF from becoming complete AFF via prophylactic internal fixation.

A case of paraspinal arteriovenous fistula in the lumbar spinal body assessed with time resolved three-dimensional phase contrast MRI.

A 93-year-old female with a paraspinal arteriovenous fistula (AVF) occurred within the lumbar spinal vertebral body was assessed with time resolved three-dimensional (3D) phase-contrast MRI (4D-Flow) on 1.5 Tesla MR scanner (GE Healthcare). The 3D vector field, streamlines, and pathlines analyses demonstrated uni-directional flow from the aorta to the large vascular cavity in the lumbar vertebral body by means of the lumbar artery as well as dilated paravertebral veins as drainers, which confirmed AVF, not aortic pseudoaneurysm. The 4D-Flow also showed an added value in planned endovascular surgery concerning localization of the precise shunting point and the shunting volume quantification.

Mandibular hematoma cells as a potential reservoir for osteoprogenitor cells in fractures.

PURPOSE: We hypothesized that cells within the mandibular fracture hematoma played an important role in mandibular fracture healing. The objective of this study was to analyze cells in human mandibular fracture hematoma. PATIENTS AND METHODS: We isolated and analyzed human mandibular fracture hematoma cells (MHCs) and investigated whether MHCs had multilineage mesenchymal differentiation capacity in vitro, similar to bone marrow stromal cells (BMSCs). RESULTS: Cell-surface markers showed that the adherent MHCs expressed mesenchymal stem cell-related markers, namely CD29, CD44, CD105, and CD166, while lacking hematopoietic markers CD14, CD34, CD45, and CD133. The proliferative potential, osteogenic potential, and adipogenic potential of MHCs were comparable to those of BMSCs. In contrast, the chondrogenic potential of MHCs was inferior to that of BMSCs. CONCLUSIONS: The role of the mandibular fracture hematoma could be as a presumptive local reservoir for osteogenic progenitors and thus contribute to intramembranous bone healing. Our findings may provide new insights into the mechanism of intramembranous bone healing in membranous bone fractures.

Altered microRNA profile during fracture healing in rats with diabetes.

BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that regulate gene expression. There is increasing evidence that some miRNAs are involved in the pathology of diabetes mellitus (DM) and its complications. We hypothesized that the functions of certain miRNAs and the changes in their patterns of expression may contribute to the pathogenesis of impaired fractures due to DM. METHODS: In this study, 108 male Sprague-Dawley rats were divided into DM and control groups. DM rats were created by a single intravenous injection of streptozotocin. Closed transverse femoral shaft fractures were created in both groups. On post-fracture days 5, 7, 11, 14, 21, and 28, miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was conducted with miRNA samples from each group on post-fracture days 5 and 11. The microarray findings were validated by real-time polymerase chain reaction (PCR) analysis at each time point. RESULTS: Microarray analysis revealed that, on days 5 and 11, 368 and 207 miRNAs, respectively, were upregulated in the DM group, compared with the control group. The top four miRNAs on day 5 were miR-339-3p, miR451-5p, miR-532-5p, and miR-551b-3p. The top four miRNAs on day 11 were miR-221-3p, miR376a-3p, miR-379-3p, and miR-379-5p. Among these miRNAs, miR-221-3p, miR-339-3p, miR-376a-3p, miR-379-5p, and miR-451-5p were validated by real-time PCR analysis. Furthermore, PCR analysis revealed that these five miRNAs were differentially expressed with dynamic expression patterns during fracture healing in the DM group, compared with the control group. CONCLUSIONS: Our findings will aid in understanding the pathology of impaired fracture healing in DM and may support the development of molecular therapies using miRNAs for the treatment of impaired fracture healing in patients with DM.

Medial clavicle pseudarthrosis successfully treated with an inverted distal clavicle locking plate.

INTRODUCTION: Medial clavicle fractures are rare injuries. Symptomatic nonunion arises up to 8% of medial clavicle fractures when treated conservatively. PRESENTATION OF CASE: A 53-year-old man sustained a left medial clavicle fracture and was treated conservatively at another hospital. Nine months after his initial injury, he was referred to our institution. We diagnosed pseudarthrosis of the medial clavicle. We performed open reduction and internal fixation using an inverted distal clavicle locking plate. At the 1-year follow-up, radiographs showed bone union. DISCUSSION: This is the first reported case of medial clavicle pseudarthrosis treated with an inverted distal clavicle anatomical locking plate. There are several advantages in using this plate. CONCLUSION: This method is a good treatment option.

Insufficiency and deficiency of vitamin D in elderly patients with fragility fractures of the hip in the Japanese population.

BACKGROUND: Data of vitamin D sufficiency in Asian patients with osteoporotic fragility hip fractures are limited. This study aimed to obtain data from the Japanese population. METHODS: Patients aged 60 years or older with hip fractures were prospectively enrolled. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured. Levels were compared between patients receiving and not receiving treatment for osteoporosis, those with and without previous contralateral hip fractures, and those with femoral neck versus trochanteric fractures. Sex-based differences were also assessed. The serum levels in patients younger than 60 years with extremity fractures were assessed, and differences between elderly and younger patients were evaluated. The individual correlation between 25(OH)D levels and the ultraviolet (UV) index and age was analyzed in elderly patients with hip fractures. RESULTS: The data of 360 patients (aged 84.7 ± 8.2 years), comprising 80 men and 280 women, were analyzed. The mean 25(OH)D level was 16.5 ± 7.2 ng/mL. The prevalence of vitamin D insufficiency (25(OH)D <30 ng/mL) and deficiency (25(OH)D <20 ng/mL) was 93.9% and 71.7%, respectively. A significant difference was noted in the prevalence of vitamin D deficiency between patients with and without previous contralateral hip fractures. Age and 25(OH)D levels were found to be correlated, with no correlation between the UV index and the 25(OH)D levels. The 25(OH)D level in the younger population (n = 123) was 20.7 ± 8.6 ng/mL, which was significantly higher than that of the elderly. CONCLUSION: Perennial vitamin D insufficiency is prevalent in elderly Japanese patients with hip fractures.

Locking plate osteosynthesis for a femoral fracture and subsequent nonunion in a patient with osteopetrosis.

INTRODUCTION: Osteopetrosis is a skeletal disorder characterized by increased osteodensity and a remodeling defect. The fragility of dense sclerotic bones may lead to an increased incidence of fractures. Although internal fixation can be performed, technical challenges may be experienced because of the increased bone density. Complications such as delayed union, nonunion, or implant failure may occur postoperatively. PRESENTATION OF CASE: We describe a patient with autosomal-dominant osteopetrosis type 2 who suffered a shaft fracture below a plate of his right femur. We performed osteosynthesis with a single locking plate. Union was delayed, and plate breakage occurred along with nonunion of the fracture. The nonunion was addressed using double locking plates, which secured fixation and allowed complete fracture healing. DISCUSSION: There were three reasons of nonunion in our case. First, we left gaps between the fragments. Second, we used mainly cerclage wires, rather than screws, for plate fixation, which led to inadequate stability. Third, the patient was large (height 167 cm, weight 93.1 kg), so the single plate provided insufficient fixing force. We then used double locking plates and attained stronger internal fixation with complete fracture healing. CONCLUSION: Double plating with locking plates may be an effective treatment option for femoral fractures in patients with osteopetrosis.

Clinical Experience With the Use of Low-Intensity Pulsed Ultrasound (LIPUS) in the Treatment of Atypical Femoral Fractures.

OBJECTIVE: The aim of this study was to report the clinical results of atypical femoral fractures (AFFs) treated with low-intensity pulsed ultrasound (LIPUS). MATERIALS AND METHODS: The data on AFFs that were surgically treated in our hospital from 2010 to 2016 was retrospectively analyzed. AFF was diagnosed based on the criteria defined by the second report of an ASBMR task force. RESULTS: Seven fractures in 6 cases were included in this study. Two fractures were referred to us as being nonunion. Five fractures were subtrochanteric fractures and 2 fractures were shaft fractures. Five fresh AFFs were fixed with an intramedullary nail and 2 nonunion fractures were fixed with plates. LIPUS was used in 6 fractures. Bone union was achieved in 5 fractures with the average time to union being 17 months (5-29). In 4 out of the 6 fractures treated with LIPUS, bone union was achieved after 14 months on average. In the other 2 LIPUS-treated fractures, bone union was not achieved even at 1 year after surgery. DISCUSSION: It is known that AFF healing tends to be very slow. Some case reports indicate that AFF healing might be accelerated by LIPUS. In the current series, the subtrochanteric fracture that was not treated with LIPUS healed at 29 months after surgery, which was much longer than the average time to union in the 5 fractures that were treated with LIPUS. Although our number of cases is small, LIPUS may be a potentially useful tool for accelerating AFF repair.