Blood loss and transfusion risk in intramedullary nailing for subtrochanteric fractures.

BACKGROUND: The incidence of hip fractures and subtrochanteric fractures in particular is increasing, along with the globally expanding aging population. Intramedullary nailing remains the 'gold standard' of their treatment. Blood loss can be a result of the original trauma, but also secondary to the subsequent surgical insult, especially during the reaming of the intramedullary canal. OBJECTIVES: The aim of our study was to report on the blood loss and incidence of blood transfusion in patients presenting with a subtrochanteric fracture treated with intramedullary nailing. Most importantly, we aim to identify factors associated with the need for transfusion within the first 48 h post-operatively. METHODS: Following institutional board approval, 431 consecutive patients (131 males; age: 79.03 years old, SD 13.68 years) presenting in a Level 1 Trauma Centre with a subtrochanteric fracture treated with an intramedullary nail were retrospectively identified, over an 8-year period. Exclusion criteria included patients with high energy injuries, pathological fractures, primary operations at other institutions and patients lost to follow-up. To identify risk factors leading to increased risk of transfusion, we first compared patients requiring intra-operative transfusion or transfusion during the first 48 h post-operatively against those who did not require transfusion. This was then followed by multivariate regression analysis adjusted for confounding factors to identify the most important risk factors associated with need for transfusion within the first 48 h post-operatively. RESULTS: Incidence of blood transfusion was 6.0% pre-operatively, compared to 62.7% post-operatively. A total of 230 patients (52.3%) required either intra-operative transfusion or transfusion during the first 48 h following surgery. Patients having a transfusion within the first 48 h post-operatively had a higher incidence of escalation in their care (p = 0.050), LOS (p = 0.015), 30-day (p = 0.033) and one-year mortality (p = 0.004). Multivariate regression analysis adjusted for confounding factors identified that the most important association of a need for transfusion within the first 48 post-operative hours was a pre-operative Hb <100 g/L (OR 6.64); a nail/canal ratio <70% (OR 3.92), followed by need for open reduction (OR 2.66). Fracture involving the lesser trochanter was also implicated with an increased risk (OR 2.08). Additionally, pre-operative moderate/severe renal impairment (OR 4.56), as well as hypoalbuminaemia on admission (OR 2.10) were biochemical predictors of an increased risk of transfusion. Most importantly, the need for transfusion was associated with an increase in 30-day mortality (OR 12.07). CONCLUSION: Several patient, fracture and surgery related factors are implicated with an increased risk for transfusion within the first 48-h post-operatively. Early identification, and where possible correction of these factors can potentially reduce blood loss and risk of transfusion, along with all the associated sequelae and mortality risk. LEVEL OF EVIDENCE: III.

Subtrochanteric femoral fractures and intramedullary nailing complications: a comparison of two implants.

INTRODUCTION: Intramedullary (IM) nails are considered the 'gold' standard treatment for subtrochanteric femoral fractures. The incidence and risk factors for re-operation in subtrochanteric fractures remain unclear. Furthermore, no studies have compared the outcomes of different nailing systems used to treat subtrochanteric fractures in the same study population. AIMS/OBJECTIVES: Our study aimed to (i) investigate the cumulative incidence and factors associated with an increased risk of re-operation in subtrochanteric fractures treated with a long intramedullary (IM) nail, (ii) compare the outcomes of subtrochanteric fractures treated with long Affixus and Gamma nails, and (iii) establish whether the addition of a proximal anti-rotation screw in the Affixus nail confers any clinical benefit. METHODS: A retrospective review of all adult patients admitted to a level 1 trauma centre with a subtrochanteric femur fracture treated with a long cephalomedullary IM nail over an 8-year period was conducted. Exclusion criteria were primary surgery performed at another institution, prophylactic nailing because of tumours, incomplete fractures, and patients who were lost to follow-up or died before fracture healing. Data variables were assessed for normality prior to determining the use of either parametric or non-parametric tests. Logistic regression analysis was performed to identify potential factors associated with re-operation. For the comparison between the two nail types, patients were matched into two groups of 119 each by age (10-year intervals), gender and mechanism of injury (low energy, high energy and pathological fractures). A p-value < 0.05 was considered significant. The Kaplan-Meier nail survival curve was used to demonstrate the survival of each nail. Data were analysed using the statistical package R (R version 3.6.0). RESULTS: A total of 309 subtrochanteric fractures were treated with a distally locked long IM nail (re-operation rate: 22.33%) over an 8-year period. Logistic regression identified six factors associated with an increased risk of re-operation, including age < 75 years old, use of a long Gamma nail, pre-injury coxa-vara femoral neck shaft angles, an immediate post-operative reduction angle of > 10° varus, deep wound infection and non-union. Following matching, we compared the two long cephalomedullary nailing systems used (Gamma versus Affixus nail). The only differences identified from the unadjusted analysis were a higher overall incidence of nail failure in Gamma nails due to any cause, re-operation, and impingement of the nail tip distally against the anterior femoral cortex. When we corrected for covariates, no significant differences remained evident between the two nails. From the Kaplan-Meier nail survival curves, however, the Affixus nail demonstrated better survivorship up to 5 years post-implantation in terms of nail failure and re-operation for all causes. Finally, the addition of a proximal anti-rotation screw in the Affixus nail did not seem to confer any benefit. CONCLUSION: We reported a 22.3% re-operation rate in our cohort of subtrochanteric fractures treated with a long IM nail. We have identified six risk factors associated with re-operation: age < 75 years old, pre-injury femoral neck shaft angle, choice of nail, varus reduction angle, fracture-related infection and non-union. The addition of a proximal anti-rotation screw in the Affixus nail did not confer any benefit.

Management of subtrochanteric femur fractures: is open reduction associated with poor outcomes?

PURPOSE: The aim of this study was to identify factors associated with the need for open reduction in subtrochanteric femoral fractures and investigate the effect of cerclage wiring compared to open reduction alone, on the development of complications, especially infection and non-union. METHODS: All consecutive patients with a fracture involving the subtrochanteric region were retrospectively identified, over an 8-year period. Data documented and analysed included patient demographics, fracture characteristics, patient comorbidities, time to fracture union and development of complications. RESULTS: A total of 512 patients met the inclusion criteria (523 fractures). Open reduction was performed in 48% (247) of the fractures. Following matching and regression analysis, we identified diaphyseal extension of the fracture to be associated with an open reduction (OR: 2.30; 95% CI 1.45-3.65; p < 0.001). Open reduction was also associated with an increased risk of superficial infection (OR: 7.88; 95% CI 1.63-38.16; p = 0.010), transfusion within 48 h following surgery (OR: 2.44; 95% CI 1.96-4.87; p < 0.001) and a prolonged surgical time (OR: 3.09; 95% CI 1.96-4.87; p < 0.001). The risk of non-union, deep infection and overall mortality was not increased with open reduction. The use of cerclage wires [50 out of 201 fractures (24.9%) treated with an open reduction] to achieve anatomical reduction as compared to open reduction alone significantly reduced the risk of non-union (OR: 0.20; 95% CI 0.06-0.74; p = 0.015). CONCLUSION: Open reduction of subtrochanteric fractures is not associated with an increased risk of deep infection and non-union, even though it is associated with an increased risk of superficial infection, prolonged surgical time and transfusion. The use of cerclage wire is associated with reduced risk of non-union with little evidence of an increase in complications. LEVEL OF EVIDENCE: III.

Anatomical reconstruction of the anterior inferior tibiofibular ligament in elite athletes using InternalBrace suture tape.

AIMS: The ideal management of acute syndesmotic injuries in elite athletes is controversial. Among several treatment methods used to stabilize the syndesmosis and facilitate healing of the ligaments, the use of suture tape (InternalBrace) has previously been described. The purpose of this study was to analyze the functional outcome, including American Orthopaedic Foot & Ankle Society (AOFAS) scores, knee-to-wall measurements, and the time to return to play in days, of unstable syndesmotic injuries treated with the use of the InternalBrace in elite athletes. METHODS: Data on a consecutive group of elite athletes who underwent isolated reconstruction of the anterior inferior tibiofibular ligament using the InternalBrace were collected prospectively. Our patient group consisted of 19 elite male athletes with a mean age of 24.5 years (17 to 52). Isolated injuries were seen in 12 patients while associated injuries were found in seven patients (fibular fracture, medial malleolus fracture, anterior talofibular ligament rupture, and posterior malleolus fracture). All patients had a minimum follow-up period of 17 months (mean 27 months (17 to 35)). RESULTS: All patients returned to their pre-injury level of sports activities. One patient developed a delayed union of the medial malleolus. The mean return to play was 62 days (49 to 84) for isolated injuries, while the patients with concomitant injuries returned to play in a mean of 104 days (56 to 196). The AOFAS score returned to 100 postoperatively in all patients. Knee-to-wall measurements were the same as the contralateral side in 18 patients, while one patient lacked 2 cm compared to the contralateral side. CONCLUSION: This study suggests the use of the InternalBrace in the management of unstable syndesmotic injuries offers an alternative method of stabilization, with good short-term results, including early return to sports in elite athletes. Cite this article: Bone Joint J 2022;104-B(1):68-75.

Development and Validation of a Post-Operative Non-Union Risk Score for Subtrochanteric Femur Fractures.

BACKGROUND: Our objective was to develop and validate a predictive model for non-union following a subtrochanteric fracture of the femur. METHODS: Following institutional board approval, 316 consecutive patients presenting to our institution (84 non-unions) who fulfilled the inclusion criteria were retrospectively identified. To identify potential unadjusted associations with progression to non-union, simple logistic regression models were used, followed by a revised adjusted model of multiple logistic regression. RESULTS: Having established the risk factors for non-union, the coefficients were used to produce a risk score for predicting non-union. To identify the high-risk patients in the early post-operative period, self-dynamisation was excluded. The revised scoring system was the sum of the following: diabetes (6); deep wound infection (35); simple or severe comminution (13); presence of an atypical fracture (14); lateral cortex gap size ≥5 mm (11), varus malreduction (5-10 degrees) (9); varus malreduction (>10 degrees) (20). On the ROC (receiver operating characteristic) curve, the area under the curve (0.790) demonstrated very good discriminatory capability of the scoring system, with good calibration (Hosmer-Lemeshow test; p = 0.291). Moreover, 5-fold cross validation confirmed good fit of the model and internal validity (accuracy 0.806; Kappa 0.416). The cut-point determined by Youden's formula was calculated as 18. CONCLUSION: This study demonstrates that the risk of non-union can be reliably estimated in patients presenting with a subtrochanteric fracture, from the immediate post-operative period. The resulting non-union risk score can be used not only to identify the high-risk patients early, offering them appropriate consultation and in some cases surgical intervention, but also informs surgeons of the modifiable surgery related factors that contribute to this risk.

Recent advances in 3D bioprinting of musculoskeletal tissues.

The musculoskeletal system is essential for maintaining posture, protecting organs, facilitating locomotion, and regulating various cellular and metabolic functions. Injury to this system due to trauma or wear is common, and severe damage may require surgery to restore function and prevent further harm. Autografts are the current gold standard for the replacement of lost or damaged tissues. However, these grafts are constrained by limited supply and donor site morbidity. Allografts, xenografts, and alloplastic materials represent viable alternatives, but each of these methods also has its own problems and limitations. Technological advances in three-dimensional (3D) printing and its biomedical adaptation, 3D bioprinting, have the potential to provide viable, autologous tissue-like constructs that can be used to repair musculoskeletal defects. Though bioprinting is currently unable to develop mature, implantable tissues, it can pattern cells in 3D constructs with features facilitating maturation and vascularization. Further advances in the field may enable the manufacture of constructs that can mimic native tissues in complexity, spatial heterogeneity, and ultimately, clinical utility. This review studies the use of 3D bioprinting for engineering bone, cartilage, muscle, tendon, ligament, and their interface tissues. Additionally, the current limitations and challenges in the field are discussed and the prospects for future progress are highlighted.

Intravascular Papillary Endothelial Hyperplasia (Masson's Tumor) Involving the Knee Synovium.

INTRODUCTION: Intravascular papillary endothelial hyperplasia or Masson's tumor is a rare benign lesion of vascular origin characterized by abnormal proliferation of endothelial cells. CASE REPORT: We present a case of this lesion involving the knee joint of a Caucasian woman who was referred to our institution for the evaluation of recurrent right knee pain. Her symptoms have started insidiously 5 years earlier following minor trauma. Recurrent symptomatic knee effusion was the cardinal symptom. Following the surgical excision of the lesion, recurrence occurred 2 years later. The tumor was successfully treated with embolization of its vascular supply. CONCLUSION: Masson's tumor involving the synovium is an uncommon condition. The intermittent symptomatology and normal appearance of biopsies taken arthroscopically during asymptomatic periods can make the diagnosis challenging. Although resection is proposed to prevent recurrence, embolization of the vascular supply of the tumor can be a viable alternative.

Vertebral body versus iliac crest bone marrow as a source of multipotential stromal cells: Comparison of processing techniques, tri-lineage differentiation and application on a scaffold for spine fusion.

The potential use of bone progenitors, multipotential stromal cells (MSCs) helping spine fusion is increasing, but convenient MSC sources and effective processing methods are critical factors yet to be optimised. The aim of this study was to test the effect of bone marrow processing on the MSC abundance and to compare the differentiation capabilities of vertebral body-bone marrow (VB-BM) MSCs versus iliac crest-bone marrow (IC-BM) MSCs. We assessed the effect of the red blood cell lysis (ammonium chloride, AC) and density-gradient centrifugation (Lymphoprep™, LMP), on the extracted VB-BM and IC-BM MSC numbers. The MSC abundance (indicated by colony counts and CD45lowCD271high cell numbers), phenotype, proliferation and tri-lineage differentiation of VB-BM MSCs were compared with donor-matched IC-BM MSCs. Importantly, the MSC attachment and osteogenesis were examined when VB-BM and IC-BM samples were loaded on a beta-tricalcium phosphate scaffold. In contrast to LMP, using AC yielded more colonies from IC-BM and VB-BM aspirates (p = 0.0019 & p = 0.0201 respectively). For IC-BM and VB-BM, the colony counts and CD45lowCD271high cell numbers were comparable (p = 0.5186, p = 0.2640 respectively). Furthermore, cultured VB-BM MSCs exhibited the same phenotype, proliferative and adipogenic potential, but a higher osteogenic and chondrogenic capabilities than IC-BM MSCs (p = 0.0010 and p = 0.0005 for calcium and glycosaminoglycan (GAG) levels, respectively). The gene expression data confirmed higher chondrogenesis for VB-BM MSCs than IC-BM MSCs, but osteogenic gene expression levels were comparable. When loaded on Vitoss™, both MSCs showed a similar degree of attachment and survival, but a better osteogenic ability was detected for VB-BM MSCs as measured by alkaline phosphatase activity (p = 0.0386). Collectively, the BM processing using AC had more MSC yield than using LMP. VB-BM MSCs have a comparable phenotype and proliferative capacity, but higher chondrogenesis and osteogenesis with or without using scaffold than donor-matched IC-BM MSCs. Given better accessibility, VB-BM could be an ideal MSC source for spinal bone fusion.

Drug-eluting implants for the suppression of metastatic bone disease: current insights.

INTRODUCTION: The fixation of impending or pathologic fractures is challenging and their successful management can have a favourable impact on the quality of life of the patient. The progression of the metastatic bone disease can cause significant pain and disability but also could result in the loosening and subsequent failure of the implants. To prevent the additional local growth, postoperative radiotherapy is often recommended, and many patients receive endocrine or chemotherapy. AREAS COVERED: Several reports support the antineoplastic drugs to bone cement as an adjuvant to improve implant stability as well as to prevent local cancer progression and failure of reconstructive devices used to treat patients with pathologic fractures. The aim of the present review is to present our current understanding on the effect of local delivery of antineoplastic drugs at the bone site. EXPERT COMMENTARY: Encouraging evidence support the application of bone cement loaded with antineoplastic drugs to fill defects and strengthen the fixation of orthopaedic implants. This is an inexpensive and safe method that can improve implant stability, prevent local cancer progression and failure of reconstructive devices. To fully evaluate its clinical effectiveness randomized clinical studies are needed.

The role of Iloprost on bone edema and osteonecrosis: Safety and clinical results.

INTRODUCTION: Iloprost is a commercially available prostaglandin I2 (PGI2) analogue that is shown to have antithrombotic, vasodilatative and antiproliferative effects. A number of clinical studies have shown that Iloprost can be effective in the management of bone marrow oedema and the treatment of avascular necrosis. The aim of this manuscript is to present our current understanding on the effect of Iloprost on the treatment of these conditions. AREAS COVERED: The authors offer a comprehensive review of the existing literature on the experimental and clinical studies analysing the effect of Iloprost on bone, bone marrow oedema and avascular necrosis. EXPERT OPINION: The available data from the clinical studies suggest that Iloprost has limited effect in advanced stages of avascular necrosis. However, literature suggests that Iloprost administration can be a viable option in the management of bone marrow oedema and early stages of osteonecrosis. Despite these promising results its effect on bone homeostasis needs further elucidation. Moreover, further data on its safety, dosage and efficiency through randomized multicenter studies are desirable in order to reach final conclusions.

Modulation of cartilage's response to injury: Can chondrocyte apoptosis be reversed?

Osteoarthritis is characterized by a chronic, progressive and irreversible degradation of the articular cartilage associated with joint inflammation and a reparative bone response. More than 100 million people are affected by this condition worldwide with significant health and welfare costs. Our available treatment options in osteoarthritis are extremely limited. Chondral or osteochondral grafts have shown some promising results but joint replacement surgery is by far the most common therapeutic approach. The difficulty lies on the limited regeneration capacity of the articular cartilage, poor blood supply and the paucity of resident progenitor stem cells. In addition, our poor understanding of the molecular signalling pathways involved in the senescence and apoptosis of chondrocytes is a major factor restricting further progress in the area. This review focuses on molecules and approaches that can be implemented to delay or even rescue chondrocyte apoptosis. Ways of modulating the physiologic response to trauma preventing chondrocyte death are proposed. The use of several cytokines, growth factors and advances made in altering several of the degenerative genetic pathways involved in chondrocyte apoptosis and degradation are also presented. The suggested approaches can help clinicians to improve cartilage tissue regeneration.

Effect of methotrexate on bone and wound healing.

INTRODUCTION: Methotrexate (MTX) is one of the most commonly used disease modifying drugs administered for wide spectrum of conditions. Through the expansion of the indications of MTX use, an increasing number of patients nowadays attend orthopaedic departments receiving this pharmacological agent. The aim of this manuscript is to present our current understanding on the effect of MTX on bone and wound healing. Areas covered: The authors offer a comprehensive review of the existing literature on the experimental and clinical studies analysing the effect of MTX on bone and wound healing. The authors also analyse the available literature and describe the incidence of complications after elective orthopaedic surgery in patients receiving MTX. Expert opinion: The available experimental data and clinical evidence are rather inadequate to allow any safe scientific conclusions on the effect of MTX on bone healing. Regarding wound healing, in vitro and experimental animal studies suggest that MTX can adversely affect wound healing, whilst the clinical studies show that lose-dose MTX is safe and does not affect the incidence of postoperative wound complications.

The role of peptides in bone healing and regeneration: a systematic review.

BACKGROUND: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. METHODS: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. RESULTS: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. CONCLUSION: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge.

Neoplasia following use of BMPs: is there an increased risk?

INTRODUCTION: Bone morphogenetic proteins are multi-functional growth factors, which play an important role in embryonic development and cellular functions. Among several molecules in this family, BMP-2 and BMP-7 are currently being used in the clinical setting. Main clinical targets include the treatment of non-union, open fractures and spinal fusion. Their use has not been without complications, one of which might be a carcinogenic effect. AREAS COVERED: The authors offer a comprehensive review of the existing literature on the clinical studies analysing the role of bone morphogenetic proteins (BMPs) on carcinogenesis. The authors analyse the available literature and describe potential signalling pathways that can be affected as per available experimental in vitro and in vivo models. EXPERT OPINION: The available experimental data and clinical evidence are rather inadequate to allow any safe scientific conclusions. Clinical studies provide incomplete evidence to support the hypothesis that BMPs are carcinogenic. The available literature has several limitations including incomplete documentation, unreported data and inhered bias as a large number of trials have been funded by the industry. The need of well-structured studies is essential to address these safety concerns.

Can we enhance fracture vascularity: What is the evidence?

Angiogenesis is a vital component of bone healing. The formation of the new blood vessels at the fracture site restores the hypoxia and nutrient deprivation found at the early stages after fracture whilst at a later stage facilitates osteogenesis by the activity of the osteoprogenitor cells. Emerging evidence suggests that there are certain molecules and gene therapies that could promote new blood vessel formation and as a consequence enhance the local bone healing response. This article summarizes the current in vivo evidence on therapeutic approaches aiming at the augmentation of the angiogenic signalling during bone repair.

Release of growth factors and the effect of age, sex, and severity of injury after long bone fracture. A preliminary report.

BACKGROUND AND PURPOSE: The systemic response after fracture is regulated by a complex mechanism involving numerous growth factors. In this study, we analyzed the kinetics of key growth factors following lower-limb long bone fracture. MATERIALS AND METHODS: Human serum was isolated from 15 patients suffering from lower-limb long bone fracture (tibia/femur) requiring surgical fixation. The levels of platelet-derived growth factor (PDGF-BB), vascular edothelial growth factor (VEGF), insulin growth factor-I (IGF-I), and transforming growth factor ß1 (TGF-ß1) were assayed by colorimetric ELISA at different time points during the first week after fracture. 10 healthy volunteers made up the control group of the study. Serum levels of the growth factors measured were compared to age, sex, and injury severity score. RESULTS: We found that there was a decline in the levels of PDGF-BB, IGF-I and TGF-ß1 during the first 3 days after fracture. However, VEGF levels remained unchanged. The levels of all the growth factors studied then increased, with the highest concentrations noted at day 7 after surgery. No correlation was found between circulating levels of growth factors and age, injury severity score (ISS), blood loss, or fluid administration. INTERPRETATION: There are systemic mitogenic and osteogenic signals after fracture. Important growth factors are released into the peripheral circulation, but early after surgery it appears that serum levels of key growth factors fall. By 7 days postoperatively, the levels had increased considerably. Our findings should be considered in cases where autologous serum is used for ex vivo expansion of mesenchymal stem cells. There should be further evaluation of the use of these molecules as biomarkers of bone union.

NSAIDS inhibit in vitro MSC chondrogenesis but not osteogenesis: implications for mechanism of bone formation inhibition in man.

The non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for analgesia but may inhibit bone formation. We investigated whether the reported NSAID effect on bone is related to inhibition of bone marrow mesenchymal stem cell (MSC) proliferation and osteogenic and chondrogenic differentiation and evaluated both cyclooxygenase (COX)-1 and COX-2 specific drugs. The effects of seven COX-1 and COX-2 inhibitors on MSC proliferation and osteogenic and chondrogenic differentiation were tested using Vybrant, sodium 3'-[1-(phenylaminocarbonyl)- 3,4-tetrazolium]-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT), functional and quantitative assays of MSC differentiation. The MSC expression of COX-1 and COX-2 and prostaglandin E2 (PGE-2) levels were evaluated serially during lineage differentiation by quantitative PCR and ELISA. None of the NSAIDs at broad range of concentration (range 10(-3) to 100 µg/ml) significantly affected MSC proliferation. Surprisingly, MSC osteogenic differentiation inhibition was not evident. However, NSAIDs affected chondrogenic potential with a reduction in sulphated glycosaminoglycans (sGAG) content by 45% and 55% with diclofenac and ketorolac, respectively (P < 0.05 compared to controls). Parecoxib and meloxicam, more COX-2 specific reagents inhibited sGAG to a lesser degree, 22% and 27% respectively (P < 0.05 compared to controls). Cartilage pellet immunohistochemistry confirmed the above results. Pellet chondrogenesis was associated with increased COX-1 expression levels but not COX-2, and COX-1 specific drugs suppressed MSC PGE-2 more than COX-2 specific inhibitors. These findings suggest that NSAIDs may inhibit bone formation via blockage of MSC chondrogenic differentiation which is an important intermediate phase in normal endochondral bone formation.

The effect of bone morphogenetic protein-2, bone morphogenetic protein-7, parathyroid hormone, and platelet-derived growth factor on the proliferation and osteogenic differentiation of mesenchymal stem cells derived from osteoporotic bone.

INTRODUCTION: It has been previously shown that in patients with osteoporosis, mesenchymal stem cell (MSC) growth rate and osteogenic potential is decreased contributing to inferior fracture consolidation. The aim of this study was to investigate the effect of bone morphogenetic protein-2 (BMP-2), BMP-7, parathyroid hormone (PTH), and platelet-derived growth factor (PDGF) on proliferation and osteogenic differentiation of MSCs derived from patients with osteoporosis. MATERIALS AND METHODS: Trabecular bone was obtained from 10 patients (four males, mean age 76 years) with lower extremity osteoporotic fractures. MSCs were isolated by enzymatic digestion. Functional assays of proliferation and osteogenic differentiation were performed under the influence of a wide range of concentrations of BMP-2, BMP-7, PTH, and PDGF-BB. Proliferation was assessed using CFU-F and XTT assays. Osteogenic differentiation was assessed by alkaline phosphatase activity and total calcium production. RESULTS: MSC proliferation was found to be stimulated by supplementation with BMP-7 and PDGF-BB, whereas BMP-2 and PTH had little effect. The largest increase in proliferation rate was observed after administration 100 ng/mL of BMP-7. All four molecules induced alkaline phosphatase activity and calcium production in growing osteoblasts with a dose-dependent effect noted. BMP-2 and BMP-7 at their highest studied concentration (100 ng/mL) produced a threefold increase in the osteogenic potential of MSCs. CONCLUSION: BMP-7, BMP-2, PTH, and PDGF-BB were observed to have a positive effect on osteogenic differentiation of MSCs. BMP-7 and PDGF-BB (in high doses) could be considered most potentially advantageous because they enhance both proliferation and osteogenic differentiation of MSCs derived from elderly osteoporotic bone.

Efficacy of minimally invasive techniques for enhancement of fracture healing: evidence today.

The successful treatment of nonunions represents a major challenge for orthopaedic surgeons. Lately, ongoing advances made in the field of molecular medicine and molecular biology have increased our understanding of the pathways and involvement of mediators surrounding the bone healing process. As a result, the surgeon's armamentarium has been increased in terms of options for intervention. This article aims to provide an overview of minimally invasive techniques applicable in the treatment of nonunions of fractures.