Antibiotic cement-coated rigid locked nails in infected femoral and tibial nonunion. Reoperation rates of commercial versus custom-made nails.

INTRODUCTION: The objective of this study is to assess bone union, infection control, and reoperation rates in a series of patients with infected femoral or tibial nonunion treated with antibiotic-cement-coated rigid nails and to compare the results obtained with custom-made nails versus commercial nails. METHODS: We retrospectively analyzed a series of consecutive patients with infected nonunion of the femur or the tibia treated with antibiotic-cement-coated rigid nails between January 2010 and 2020. We assessed patients' distinctive characteristics, initial injury, type of nail used (custom-made nail with vancomycin or commercial nail with gentamicin), success rate (bone union + infection control), reoperation rate, and failure rate. Comparative analyses were conducted between reoperated and non-reoperated patients regarding the type of nail used. A multivariate regression analysis was performed to assess the risk variables that impacted reoperation rates. RESULTS: We included 54 patients with 22 (40.74%) infected femoral nonunions and 32 (59.25%) tibial nonunions, who were treated with 38 (70.37%) custom-made antibiotic-cement coated nails and 16 (29.62%) commercial nails. Bone union and infection control were achieved in 51 (94.44%) cases. The reoperation rate was 40.74% (n = 22), and the failure rate was 5.55% (n = 3). The use of custom-made nails was associated with a higher risk of reoperation (Odds Ratio 4.71; 95% Confidence Interval 1.10 - 20.17; p = 0.036). CONCLUSION: Antibiotic-cement-coated nails reached a 94.44% success rate. Nails manufactured in the OR coated with vancomycin cement were associated with a higher risk of reoperation than commercial nails loaded with gentamicin cement. LEVEL OF EVIDENCE: III comparative, observational, non-randomized.

Bone Morphogenic Protein for Upper Extremity Fractures: A Systematic Review.

BACKGROUND: This review discusses success, time to healing, and complications of bone morphogenic proteins (BMPs) 7 and 2 in treating upper extremity nonunions. METHODS: Systematic review identified 26 of 479 studies that met inclusion criteria. Publications described application of BMPs to acute and chronic upper extremity delayed unions/nonunions. Unions, complications, patient demographics, and fracture/healing patterns were pooled and analyzed. RESULTS: Nonunions treated with BMP-7 (n=302) involved the humerus (64%), forearm (22%), clavicle (11%), and hand/wrist (3%), with prior surgical correction attempted in 84%. Nonunions treated with BMP-2 (n=96) involved the humerus (58%), hand/wrist (27%), forearm (14%), and clavicle (1%), with prior surgical correction attempted in all. Most nonunions (80%) were present for over 12 months before BMP application. Union rates of BMP-7 varied according to site: hand/wrist (95%), humerus (74%), forearm (29%), and clavicle (6.2%) nonunions achieved union as defined by study authors in 232 days (confidence interval=96-369, Q<0.001) on average. While not significant across studies, BMP-2 union rates were 71% of hand/wrist and 75% of humerus nonunions. Comparison of the BMPs demonstrates different proportions of success in humerus and hand/wrist fractures (P<.001) but not forearm fractures (P<.77) and longer time to radiographic union with BMP-7 (P<.011). CONCLUSIONS: Most hand/wrist and humerus nonunions treated with BMP-7 and BMP-2 achieved union, with significant similarity among BMP-7 studies not observed in BMP-2 studies. Nonunions treated with BMP-7 have longer healing times yet similar complication rates compared with BMP-2. Overall, BMPs are an effective adjunct to fracture healing with acceptable complication profile.

Long-Term Assessment of Bone Regeneration in Nonunion Fractures Treated with Compression-Resistant Matrix and Recombinant Human Bone Morphogenetic Protein-2 in Dogs.

OBJECTIVE: The aim of this study was to assess bone density, bone architecture and clinical function of canine nonunion distal appendicular long bone fractures with a defect treated with fixation, compression-resistant matrix and recombinant human bone morphogenetic protein-2 (rhBMP-2). STUDY DESIGN: Prospective cohort study with dogs at least 1-year post treatment. Computed tomography was performed and quantitative measurements from previous fracture sites were compared with measurements from contralateral limbs. Subjective evaluation included gait assessment and palpation. RESULTS: Six patients met the inclusion criteria. The rhBMP-2 treated bone exhibited higher density at the periphery and lower density in the centre, similar to the contralateral limb. All patients were weight bearing on the treated limb and all fractures were healed. CONCLUSION: The rhBMP-2-treated bone underwent restoration of normal architecture and density. Acceptable limb function was present in all patients. The results of this study can serve as a basis for long-term response in treating nonunion fractures in veterinary patients.

An Audit of the effect of Bone Morphogenetic Protein-2 Treatment in patients with non-union of long bone fractures.

OBJECTIVE: To evaluate the outcomes, clinical and radiological application of Bone Morphogenetic Protein-2 alone versus Bone Morphogenetic Protein-2 with autograft in long bone non-unions. METHODS: A prospective review of patients was done with fracture non-union admitted to Aga Khan University Hospital, Karachi, from January 2016 to January 2019. The patients were divided into two groups; those exposed to Bone Morphogenetic Protein-2 alone in group 1, and those exposed to Bone Morphogenetic Protein-2 plus autologous graft in group 2. RESULTS: Background characteristics of both the groups were analysed. Patients were followed up at 6, 12 and 24 weeks through their medical records. The primary outcome was postoperative union at 6, 12 and 24. Union was defined by having the clinical union as well as the radiological union at the same time of assessment. Of the 80 patients enrolled, 13(16.25%) were excluded, and 5(6.25%) were lost to follow-up. The final sample had 62(77.5%) patients; 35(56.5%) in group 1, and 27(43.5%) in group 2. Union at 6 weeks was observed in 13(21%) patients; 8(62%) in group 1, and 5(38%) in group 2. Union at 12 weeks was observed in 38(61%) patients; 20(53%) in group 1, and 18(47%) in group 2. CONCLUSIONS: Results showed that using the adjuvant treatment alone was not worse than using it along with bone autologous graft.

Teriparatide as an Effective Nonsurgical Treatment for a Patient with Basicervical Peritrochanteric Fracture Nonunion-A Case Report.

The nonunion rate of surgically treated basicervical peritrochanteric fractures has been reported to be as high as 9%. Due to the high 1-year mortality rate following revision surgery, finding an effective nonsurgical treatment option is of interest. Over the last decade, numerous reports have been published that have suggested teriparatide as an effective treatment for certain types of fracture nonunion. However, the literature focused on teriparatide treatment for proximal femoral fracture nonunion is scanty. A 70-year-old man suffering from a left hip basicervical peritrochanteric fracture received cephalomedullary nail fixation. Nine months after the surgery, the patient still complained of left hip pain referring to the medial thigh with an antalgic limping gait. No sign of healing was noted for more than a consecutive 3 months of follow-up. Fracture nonunion was diagnosed and further confirmed by the computed tomography (CT). The patient preferred nonsurgical treatment after thorough discussion. He then received 4 months of subcutaneous teriparatide injections, 20 mcg daily. After less than 4 months of teriparatide treatment, a follow-up CT confirmed fracture union and the patient's pain subsided. The patient also tolerated independent ambulation afterward. Teriparatide has been reported to be an effective treatment for certain types of fracture nonunion. Our case goes a step further to expand its possible application for basicervical peritrochanteric fracture nonunion. However, further larger scale studies are needed to confirm its efficacy.

The intersection of fracture healing and infection: Orthopaedics research society workshop 2021.

Infection is a common cause of impaired fracture healing. In the clinical setting, definitive fracture treatment and infection are often treated separately and sequentially, by different clinical specialties. The ability to treat infection while promoting fracture healing will greatly reduce the cost, number of procedures, and patient morbidity associated with infected fractures. In order to develop new therapies, scientists and engineers must understand the clinical need, current standards of care, pathologic effects of infection on fractures, available preclinical models, and novel technologies. One of the main causes of poor fracture healing is infection; unfortunately, bone regeneration and infection research are typically approached independently and viewed as two separate disciplines. Here, we aim to bring these two groups together in an educational workshop to promote research into the basic and translational science that will address the clinical challenge of delayed fracture healing due to infection. Statement of clinical significance: Infection and nonunion are each feared outcomes in fracture care, and infection is a significant driver of nonunion. The impact of nonunions on patie[Q2]nt well-being is substantial. Outcome data suggests a long bone nonunion is as impactful on health-related quality of life measures as a diagnosis of type 1 diabetes and fracture-related infection has been shown to significantly l[Q3]ower a patient's quality of life for over 4 years.  Although they frequently are associated with one another, the treatment approaches for infections and nonunions are not always complimentary and cannot be performed simultaneously without accepting tradeoffs. Furthermore, different clinical specialties are often required to address the problem, the orthopedic surgeon treating the fracture and an infectious disease specialist addressing the sources of infection. A sequential approach that optimizes treatment parameters requires more time, more surgeries, and thus confers increased morbidity to the patient. The ability to solve fracture healing and infection clearance simultaneously in a contaminated defect would benefit both the patient and the health care system.

The Fate of Patients After a Staged Nonunion Procedure for Known Infection.

OBJECTIVES: To determine the factors associated with successful union and eradication of infection in the setting of staged procedures to treat obviously infected nonunions of long bones. We hypothesize that patients with positive intraoperative cultures obtained at the time of definitive surgery for infected nonunions are more likely to have persistent nonunion than those with negative cultures. DESIGN: Multicenter retrospective review. SETTING: Eight academic Level 1 trauma centers. PATIENTS/PARTICIPANTS: Patients who underwent staged management for obviously infected nonunion of a long bone. MAIN OUTCOME MEASUREMENTS: For each patient, initial fracture management, management of retained implants, number of debridements, grafting, bacteriology, antibiotic course, bone defect management, soft-tissue coverage, and definitive surgery performed were reviewed. RESULTS: A total of 134 patients were treated with staged procedures for obviously infected nonunion of a long bone (mean age 49 years, 60% open fractures, and mean follow-up 22 months). During definitive procedures, 120 patients had intraoperative cultures taken with 43% having positive cultures. For culture-positive patients, 41 patients achieved eventual union and 10 had persistent nonunion. Of 69 culture-negative patients, 66 achieved eventual union and 3 had persistent nonunion. The number of patients with union versus persistent nonunion was statistically significant between culture-positive and culture-negative groups (P = 0.015). CONCLUSIONS: Management of infected nonunion in long bones with staged treatments before definitive fixation are beneficial but ultimately less effective when performed in the setting of positive bacterial cultures at the time of definitive management. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Clinicoradiological outcomes following single-stage treatment using external fixator, copious bone grafting and high dose antibiotics for infected postosteomyelitic nonunion of femoral shaft.

We aimed to study clinical and radiological outcomes following a 'single-stage protocol' in postosteomyelitic-infected nonunion of the femur in children. The report is based on a retrospective chart review (2010-2018) of 10 children below 12 years of age presenting with nonunion following a pathological fracture after osteomyelitis of hematogenous origin treated with above-mentioned operative modality. All patients were grade A (normal host) on the basis of the physiological classification. Patients with posttraumatic or surgical osteomyelitis were excluded. All patients were treated with a combination of debridement of dead bone and necrotic tissues, acute bone docking, use of external fixator and addition of copious nonvascularized autogenous bone graft obtained from fibula/tibia. The postsurgical period was covered by high dose broad spectrum antibiotics for 6 weeks. At follow up, union, infection, deformity, leg-length discrepancy, motion of hip and knee and ability to perform unaided walking was recorded. Mean age for studied patients (five males and five females) was 6.6 years. Average time elapsed since pathological fracture was 7.7 months (range: 3-15 months). MRSA and MSSA were cultured in three and four patients, respectively. Union occurred in all patients with average time of 3.7 months and total follow up being 2.9 years (range: 1-7 years). There was persistence of deep infection despite union in three patients. Average limb shortening was 4.3 cm (range: 2-7 cm). The knee motion was severely restricted (≤30°) in three patients. According to Paley's criteria, there were 2 excellent, 4 good, 2 fair and 2 poor results. Single-stage protocol as described above is a usable option for postosteomyelitic femoral nonunions in children. Union occurred in all cases. Healing occurred in three patients despite the persistence of infection. The restriction of range of motion at knee and limb length discrepancy was main complication encountered with this procedure.

Treatment of Chronic Nonunion of a Sternal Fracture With Teriparatide.

Chronic nonunion of sternal fractures is typically treated by osteosynthesis plating with or without autologous bone grafting. Described here is a case of the successful use of teriparatide, a bone-forming drug currently used for the treatment of severe osteoporosis, in the healing of a sternal nonunion fracture occurring after blunt thoracic trauma.

[Platelet-rich plasma injection for the treatment of atrophic fracture nonunion].

OBJECTIVE: To explore clinical effects of platelet rich plasma (PRP) injection in treating atrophic fracture nonunion. METHODS: From March 2015 to March 2017, 15 patients with atrophic fracture nonunion were treated with PRP injection, including 10 males and 5 females, aged from 23 to 56 years old with an average age of (40.0±9.1) years old, the time of fracture nonunion ranged from 6 to 14 months with an average of (8.87±2.45) months. Preparing PRP by extracting 60 to 100 ml peripheral blood. PRP platelet count ranged from 587 to 1 246 with an average of (947.13±158.58) ×10 9 /L. Under the perspective, 13 to 20 ml PRP were injected into the fracture end, and each injection was performed once on the first and the second week of the treatment. Complications such as whether the limb was shortened, angulation, and rotational deformity and radiological examination were observed. RESULTS: All patients were followed up from 6 to 12 months with an average of (6.8± 2.1) months. No shortening, angulation, and rotational deformity occurred. Thirteen patients had fracture healing, the time ranged from 4 to 6 months with an average of (4.8±0.7) months. Two patients had no completely porosis at 12 months during following up, and 1 patient occurred bolt loose. Other patients had no complications. CONCLUSION: The stability of fracture ends of atrophic fracture nonunion after internal fixation is an indication for local PRP injection. PRP treatment for atrophic fractures could completed under local anesthesia, and it has advantages of safe operation and reliable efficacy.

Successful treatment for bilateral femoral neck insufficiency fractures: a rare lesion case report and an updated review of the literature.

BACKGROUND: The incidence of insufficiency fracture (IF) at femoral neck is low, accounting for about 5% of all insufficiency fractures, and IF at bilateral femoral neck is less common with more occurrence in athlete or serviceman. With the aging of populations, more cases of bilateral femoral neck IF have occurred recently, while the standard clinical treatment still remains lacking due to the complexity of these patients. CASE PRESENTATION: A 55-year-old male patient complained pain in his bilateral hip, with no history of trauma, glucocorticoid hormone consumption or radiotherapy, and imaging examination revealed fracture nonunion and shortening in his left femoral neck, and double fracture line on the right femoral neck. The patient received a cementless THA for the left femoral neck fracture and conservative treatment for the right side, followed by Elcatonin injection and oral administration of Carbonate D3 Granules. After 4 months of fellow-up, the patient presented improved functional scorings in bilateral hip joints, with no signs of prothesis infection or loosening. CONCLUSION: We present a rare case of bilateral femoral neck IF in a middle-aged male and the treatment is successful. The timely CT and MRI examinations of bilateral hip joints for patients was necessary for orthopedists to select proper therapeutic regimen. In addition, the choice for therapeutic regimen of bilateral femoral IF should not only be based on the professional judgement of orthopedists, but also on the wishes of patients.

Preclinical biological and physicochemical evaluation of two-photon engineered 3D biomimetic copolymer scaffolds for bone healing.

A major challenge in orthopedics is the repair of large non-union bone fractures. A promising therapy for this indication is the use of biodegradable bioinspired biomaterials that stabilize the fracture site, relieve pain and initiate bone formation and healing. This study uses a multidisciplinary evaluation strategy to assess immunogenicity, allergenicity, bone responses and physicochemical properties of a novel biomaterial scaffold. Two-photon stereolithography generated personalized custom-built scaffolds with a repeating 3D structure of Schwarz Primitive minimal surface unit cell with a specific pore size of ∼400 µm from three different methacrylated poly(d,l-lactide-co-ε-caprolactone) copolymers with lactide to caprolactone monomer ratios of 16 : 4, 18 : 2 and 9 : 1. Using in vitro and in vivo assays for bone responses, immunological reactions and degradation dynamics, we found that copolymer composition influenced the scaffold physicochemical and biological properties. The scaffolds with the fastest degradation rate correlated with adverse cellular effects and mechanical stiffness correlated with in vitro osteoblast mineralization. The physicochemical properties also correlated with in vivo bone healing and immune responses. Overall these observations provide compelling support for these scaffolds for bone repair and illustrate the effectiveness of a promising multidisciplinary strategy with great potential for the preclinical evaluation of biomaterials.

Nandrolone decanoate in induced fracture nonunion with vascular deficit in rat model: morphological aspects.

BACKGROUND: The nonunion fracture is a relatively frequent complication in both human and veterinary medicine. Specifically, atrophic fracture nonunions are difficult to treat, with revision surgery usually providing the best prognosis. Anabolic steroids, such as nandrolone decanoate (ND), have been reported to have beneficial clinical effects on bone mass gain during osteoporosis; however, their utility in promoting regeneration in atrophic nonunions has not been documented. Our objective was to examine morphological changes induced by the ND in experimental fracture nonunion with vascular deficit in the rat model. METHODS: Fourteen adult Wistar rats had an atrophic fracture nonunion induced in the diaphysis of their left femur. Rats were allocated into two groups: control group and nandrolone decanoate group. Rats in the latter group were given nandrolone decanoate (1.5 mg/kg IM, once a week, during 4 weeks after confirmation of fracture nonunion radiographically). Radiographic and anatomopathological examination, micro-tomography and histological analysis were assessed to characterize the morphological changes promoted by the nandrolone decanoate use. RESULTS: Based on radiology, anatomopathological evaluation, computed micro-tomography and conventional microscopy, nandrolone decanoate promoted bone regeneration at the fracture nonunion site by increasing the cellularity at the fracture site. Percentage of collagen was not significantly different between groups, consistent with high-quality regenerated bone. CONCLUSION: The anabolic steroid nandrolone decanoate improved bone mass and regeneration without affecting collagen production and therefore has potential for improving outcomes for atrophic fracture nonunion.

Use of Masquelet technique in treatment of septic and atrophic fracture nonunion.

BACKGROUND: Treatment of atrophic non-unions and large bone defects or infections remains a challenging task for the treating surgeon. In the herein study, we present our experience of the 'Masquelet technique' according to the 'diamond concept' for the treatment of complex long bone reconstruction procedures. METHODS: Between February 2010 and March 2015, 150 patients (mean age 51.4) with atrophic and- /or infected non-unions were included in this prospective study. All patients received autologous bone graft, a graft expander (TCP (tricalcium phosphate)) and BMP (bone morphogenic protein). Clinical and radiological parameters were assessed at 6 weeks, and at 3, 6 and 12 months. The SF-12 questionnaire was used to evaluate the subjective health of patients. RESULTS: A successful bony consolidation of the non-unions was observed in 120 (80%) cases with a median healing time of 12.1 months. The mean defect gap was 4.4cm. Initial infection was documented in 54 cases. The most frequently identified pathogen was staphylococcus epidermidis and staphylococcus aureus. A successful removal of microorganisms with subsequent healing was achieved in 39 cases (72%). The SF-12 scores of subjective physical and mental health increased from PCS 31.5 preoperatively to 36.7 one year postoperatively, while MCS increased from 45.5 to 48.7. CONCLUSIONS: Our study showed that the Masquelet technique according to the 'diamond concept' is a valid method to treat complex atrophic non-unions with large bone defects and associated infection. Following the principles of the 'diamond concept' (targeted optimization of tissue engineering and bone regeneration) a high rate of success can be expected in these difficult reconstruction cases.

MiR-539-5p negatively regulates migration of rMSCs induced by Bushen Huoxue decoction through targeting Wnt5a.

Bone fractures are very common, and above 5% of the fractures are impaired, leading to nonunions and severe disablilities. The traditional Chinese medicine Bushen Huoxue decoction (BHD) has been used to treat fracture in China. Our previous report has found that BHD promotes migration of rat mesenchymal stem cells (rMSCs) by activating Wnt5a signaling pathway. However, whether and how miRNAs are involved in modulating rMSCs migration induced by BHD has not been explored. In the present study, miRNA microarray analysis and further validation by real-time quantitative RT-PCR revealed that miR-539-5p was down-regulated in BHD-induced rMSCs. Transfection of miR-539-5p mimics suppressed rMSCs migration while the miR-539-5p inhibitor promoted rMSCs migration. Our results suggested that miR-539-5p was a negative regulator of migration of rMSCs induced by BHD. Target prediction analysis tools and Dual-luciferase reporter gene assay identified Wnt5a as a direct target of miR-539-5p. MiR-539-5p inhibited the expression of the Wnt5a and its downstream signaling molecules including JNK, PKC and CaMKII, which played a critical role in regulating migration of rMSCs. Taken together, our results demonstrate that miR-539-5p negatively regulates migration of rMSCs induced by BHD through targeting Wnt5a. These findings provide evidence that miR-539-5p should be considered as an important candidate target for the development of preventive or therapeutic approaches against bone nonunions.

VEGF-loaded mineral-coated microparticles improve bone repair and are associated with increased expression of epo and RUNX-2 in murine non-unions.

A poor vascular supply of the fracture gap is a key factor for the development of atrophic non-unions. Mineral-coated microparticles (MCM) represent a sophisticated carrier system for the delivery of vascular endothelial growth factor (VEGF). Hence, we investigated whether VEGF-loaded MCM improve bone repair in non-unions. For this purpose, we analyzed binding and release kinetics of MCM for VEGF in vitro. Moreover, we applied VEGF-loaded or -unloaded MCM in a murine non-union model in vivo and studied the process of bone healing by means of biomechanical, radiological, histomorphometric, and Western blot techniques. MCM-free non-unions served as controls. The binding efficiency of MCM for VEGF was 46 ± 3% and the release profile revealed an initial minor burst release followed by a sustained release over a 50-day study period, thus, mimicking the physiological expression profile of VEGF during bone healing. In vivo, bone defects treated with VEGF-loaded MCM exhibited a higher bending stiffness, a higher fraction of bone volume/tissue volume and a larger callus area on days 14 and 70 when compared to the other groups. Western blot analyses on day 14 revealed a higher expression of VEGF, erythropoietin (EPO), and runt-related transcription factor 2, but not of EPO-receptor in bone defects treated with VEGF-loaded MCM. These findings demonstrate that the use of MCM for VEGF delivery shows great potential due to the ability to maintain protein stability and functionality in vivo. Moreover, the application of VEGF-loaded MCM represent a promising strategy for the treatment of non-unions. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Therapy of aseptic nonunions with parathyroid hormone.

The absence of osseous consolidation of a fracture for 9 or more months with no potential to heal is defined as nonunion. Both for the patient and from a socioeconomic point of view, nonunions represent a major problem. Hypertrophic, vital nonunions are distinguished from atrophic avital ones. Risk factors for a delayed fracture healing are insufficient immobilisation, poor adaptation of the fracture surfaces or residual instability, interposition of soft tissue within the fracture gap, as well as circulation disturbances and infections. The incidence of nonunions after fractures of the long bones lies between 2.6 and 16% depending on the surgical technique used. In human and animal studies, a positive effect of parathyroid hormone (PTH) on fracture healing has been shown. PTH has a direct stimulatory effect on osteoblasts and osteoclasts. In addition, it appears to influence the effect of osseous growth factors. In this prospective study, 32 patients with nonunions were treated with teriparatide to investigate the effects of PTH on fracture healing. Definitive healing of the nonunions following PTH treatment could be observed in 95% of the cases.

Parathyroid hormone for bone regeneration.

Delayed healing and/or non-union occur in approximately 5-10% of the fractures that occur annually in the United States. Segmental bone loss increases the probability of non-union. Though grafting can be an effective treatment for segmental bone loss, autografting is limited for large defects since a limited amount of bone is available for harvest. Parathyroid hormone (PTH) is a key regulator of calcium homeostasis in the body and plays an important role in bone metabolism. Presently PTH is FDA approved for use as an anabolic treatment for osteoporosis. The anabolic effect PTH has on bone has led to research on its use for bone regeneration applications. Numerous studies in animal models have indicated enhanced fracture healing as a result of once daily injections of PTH. Similarly, in a human case study, non-union persisted despite treatment attempts with internal fixation, external fixation, and autograft in combination with BMP-7, until off label use of PTH1-84 was utilized. Use of a biomaterial scaffold to locally deliver PTH to a defect site has also been shown to improve bone formation and healing around dental implants in dogs and drill defects in sheep. Thus, PTH may be used to promote bone regeneration and provide an alternative to autograft and BMP for the treatment of large segmental defects and non-unions. This review briefly summarizes the unmet clinical need for improved bone regeneration techniques and how PTH may help fill that void by both systemically and locally delivered PTH for bone regeneration applications. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2586-2594, 2018.

Outcomes of Presumed Aseptic Long-Bone Nonunions With Positive Intraoperative Cultures Through a Single-Stage Surgical Protocol.

OBJECTIVE: To evaluate the outcomes of a single-stage surgical protocol to treat a presumed aseptic long-bone nonunion with positive intraoperative cultures obtained at the time of surgery. DESIGN: Retrospective comparative series. SETTING: Orthopaedic specialty hospital. PATIENTS AND METHODS: We retrospectively identified 77 patients with long-bone nonunions thought to be aseptic preoperatively, which grew bacteria from cultures obtained at the time of index nonunion surgery. INTERVENTION: Fifty (65%) patients underwent open debridement of the nonunion site followed by surgical stabilization through plates and screws. Twenty-seven (35%) patients underwent exchange nailing with canal reamings used for cultures. MAIN OUTCOME MEASUREMENT: Rate of radiographic union, time to clinical and radiographic union, nonunion rate after index nonunion surgery, and final union rate after revision procedures. RESULTS: Osseous union after the index nonunion surgery was achieved in 84% of the patients (65 of 77). Time to clinical union was 6.3 months (range, 1-24 months), and time to radiographic union was 7.4 months (range, 2-24 months). Eighteen percent (14 of 77 patients) did not heal after the index nonunion surgery and required additional surgeries. The final union rate after revision surgery was 99% (76 of 77 patients). CONCLUSIONS: Eighty-four percent of presumed aseptic nonunions of long-bone fractures with positive intraoperative cultures fully healed after a single-stage surgical protocol and long-term antibiotic when appropriate. When patients are diagnosed with a subclinical infected nonunion, they should be counseled about the higher likelihood of reoperation, but in most cases can expect excellent union rates after 1 additional surgery. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.