Achieving Bone Healing Non-Operatively in Humeral Fractures in Two Patients with Risk Factors for Nonunion Utilizing a Specialized Orthosis.

We report the treatment of two patient with humeral fractures with one or more risk factors for nonunion. The first patient was elderly with a previously diagnosed central nervous sys-tem injury. The second elderly patient previously sustained a cerebral vascular accident affecting the fractured arm. The fracture was oblique in the proximal third of the humerus. We achieved bone healing non-operatively utilizing a spe-cialized plastic orthosis that included a deforming element made of dense foam. This device asymmetrically increases the soft tissue pressure around the fracture.

InSafeLOCK® humeral nailing for humeral nonunions: Clinical and radiological results.

OBJECTIVES: This study aims to evaluate the clinical and functional results of patients treated with InSafeLOCK® humeral nail and iliac crest autograft for humeral nonunion. PATIENTS AND METHODS: A total of 15 patients (11 males, 4 females; mean age: 52.1±15.3 years; range, 31 to 78 years) who were followed conservatively for humeral fractures and operated with the InSafeLOCK® humeral nail and iliac bone graft in our center between June 2018 and January 2020 were retrospectively analyzed. Data including demographic and clinical characteristics of the patients, operative data, and pre- and postoperative Visual Analog Scale (VAS), Disabilities of the Arm, Shoulder, and Hand (DASH), and Constant-Murley Scores (CMS) were recorded. RESULTS: The mean time from injury to nonunion treatment was 10.9±1.6 months. Five patients had atrophic, eight patients had oligotrophic, and two patients had hypertrophic nonunion. Preoperatively, the mean DASH was 37.7±9.1, the mean CMS was 69.7±6.3, and the mean VAS was 3.8±0.7. In all patients, union was achieved. The mean operation time was 59.0±16.2 min. The mean postoperative DASH score was 16.1±8.7, CMS 87.4±3.4, and VAS score 0.8±0.7. Regarding the shoulder joint, the mean abduction was 164.7±11.3 degrees, the mean internal rotation was 82.0±6.8 degrees, the mean external rotation was 81.3±8.3 degrees, and the mean flexion was 162.0±12.1 degrees. During follow-up, complications such as vascular-nerve injury, reflex sympathetic dystrophy, screw migration or loosening, implant failure, and loss of reduction did not occur in any of our patients. CONCLUSION: Considering the satisfactory functional and radiological results, the InSafeLOCK® humeral nail can be used safely in humeral nonunions.

Assessment of Lower Limb Load Distribution in Patients Treated with the Ilizarov Method for Tibial Nonunion.

BACKGROUND Successful treatment of tibial nonunion should lead to a complete bone union, lack of pain, and pathological mobility of the lower extremity, as well as to the achievement of satisfactory joint mobility and muscle strength, which in turn improves its biomechanics. The objective of this study was to assess the load placed on the lower limbs in patients subjected to treatment with the Ilizarov method due to aseptic tibial nonunion. MATERIAL AND METHODS This research involved 24 participants (average age, 55 years). All were diagnosed with aseptic tibia nonunion and treated with the Ilizarov external fixator between 2000 and 2017. The control group was matched to the treated group in terms of sex and age. This study used pedobarography evaluation to assess lower limb load distribution. RESULTS No differences were found in the distribution of the load over the entire foot or of the forefoot and hindfoot of the treated limb in comparison to the non-dominant limb of the controls, or in the healthy limb of the treated group compared to the dominant limb of the control group. Similarly, differences in load distribution between the operated and healthy limbs of the treated group were insignificant. CONCLUSIONS Patients subjected to treatment with the Ilizarov external fixator for aseptic tibial nonunion show symmetrical load distribution on both lower limbs following treatment, which does not differentiate them in this respect from healthy individuals. Treated patients presented with a symmetrical distribution of the load on the lower extremities over the entire foot surface, including the forefoot and hindfoot. Finally, the Ilizarov external fixator enables restoration of correct static biomechanics of the treated limbs over the period of aseptic tibial nonunion therapy.

Development of a tibial experimental non-union model in rats.

BACKGROUND: Many non-union animal models have been developed to explore the problems surrounding fracture healing. However, the existing models are not perfect and cannot satisfy all non-union studies. This study aimed to make a non-union model of the tibia in rats by cauterization of the posterior of 2 mm on both sides of the fracture end after open osteotomy of the tibia and fixing the fractured tibia with a Kirschner wire 0.8 mm in diameter. METHODS: For this study, 96 female adult Sprague-Dawley (SD) rats were used. The rats underwent surgery to produce a tibial open fracture and were fixed with a 0.8-mm diameter Kirschner wire. In 48 of the rats, the periosteum proximal and distal to the fracture end was cauterized. RESULTS: At 2, 4, 6, and 8 weeks after surgery, radiological and histological analysis showed typical physiological healing in the control group, and the healing rate was 100% at 6 weeks. But the non-union group was characterized by resorption of the fracture ends with few callus formations and no bridging callus formation, and the healing rate was 0% at 8 weeks. CONCLUSIONS: This method represents a reproducible model to create atrophic non-unions. This model provides a new option for studying the basic healing mechanisms and evaluating new therapies for bone regeneration and treatment of non-unions.

Early systemic immune biomarkers predict bone regeneration after trauma.

Severe traumatic injuries are a widespread and challenging clinical problem, and yet the factors that drive successful healing and restoration of function are still not well understood. One recently identified risk factor for poor healing outcomes is a dysregulated immune response following injury. In a preclinical model of orthopedic trauma, we demonstrate that distinct systemic immune profiles are correlated with impaired bone regeneration. Most notably, elevated blood levels of myeloid-derived suppressor cells (MDSCs) and the immunosuppressive cytokine interleukin-10 (IL-10) are negatively correlated with functional bone regeneration as early as 1 wk posttreatment. Nonlinear multivariate regression also implicated these two factors as the most influential in predictive computational models. These results support a significant relationship between early systemic immune responses to trauma and subsequent local bone regeneration and indicate that elevated circulating levels of MDSCs and IL-10 may be predictive of poor functional healing outcomes and represent novel targets for immunotherapeutic intervention.

Repurposing denosumab for recalcitrant bone healing.

Fracture healing has four phases: haematoma formation, soft callus, hard callus and remodelling. Often, non-healing fractures have an arrest of one of these phases, which need resurgery. We have repurposed denosumab for impaired fracture healing cases to avoid surgical intervention. Here, we report a series of three cases of impaired fracture healing where denosumab was given 120 mg subcutaneous dosages for 3 months to enhance healing. All the three cases have shown complete bone union at a mean follow-up of 6.7 months (5-9 months) as assessed clinically and radiologically, and have observed no adverse effect of the therapy. Denosumab given in this dose aids fracture healing by increasing callus volume, density and bridges the fracture gap in recalcitrant fracture healing cases where the callus fails to consolidate.

Case series and finite element analysis of PFNA combined with cerclage wire for treatment of subtrochanteric fracture of femur.

OBJECTIVE: To retrospectively analyze the clinical efficacy of PFNA combined with a cerclage wire in the treatment of 52 patients with unstable subtrochanteric fracture of the femur and to analyze the biomechanical effect of ligature on a fracture model. METHODS: In this study, 52 patients with unstable subtrochanteric fractures were treated in our orthopedic trauma center from June 2013 to July 2018. The Seinsheimer type IV fracture model was established using the patient's CT data, and the joint surface of the distal femoral condyle and the external condyle were restrained. The femoral head was used as the loading point, and a force of 500 N was applied vertically along the long axis of the femoral shaft. RESULTS: All 52 patients were followed up for 12 to 37 months, with an average of 18.07 ± 4.38 months. According to the Sanders hip function score, 28 cases were excellent (55-60 points), 22 cases were good (45-54 points), and 2 cases were poor (35-44 points), with an excellent and good rate of 96.15%. Postoperative deep vein thrombosis occurred in 3 cases, and fracture nonunion occurred in 1 case. No infection, loose fracture of internal fixation or hip varus deformity occurred. The finite element analysis indicated that the displacement of the whole model decreased slightly and the relative sliding of the fracture block decreased, but the maximum stress of the femur increased after the addition of the cerclage wire. CONCLUSION: The treatment of unstable subtrochanteric fracture of the femur with PFNA combined with cerclage wire has the advantages of simple operation, satisfactory reduction of fracture, stable fixation, and good recovery of limb function. The finite element analysis suggested that the biomechanical strength fixation was enhanced after the addition of cerclage wire. However, the local stress concentration of the tie may increase the risk of failure.

Minimal Pain Decrease Between 2 and 4 Weeks After Nonoperative Management of a Displaced Midshaft Clavicle Fracture Is Associated with a High Risk of Symptomatic Nonunion.

BACKGROUND: The main long-term benefit of operative treatment of displaced midshaft clavicular fractures is the reduction in nonunion risk, and as this risk is generally low, the ideal approach would be to operate only patients at high risk of nonunion. However, most current surgical decision models use baseline variables to estimate the nonunion risk, and the value of these models remains unclear. Pain in the early weeks after fracture could be potentially be an indirect measurement of fracture healing, and so it is a potential proxy variable that could lead to simpler prediction models. QUESTIONS/PURPOSES: (1) Is pain a possible proxy variable for the development of symptomatic nonunion after nonoperative treatment of midshaft clavicular fractures? (2) How reliable is the model we created that uses pain as a proxy variable for symptomatic nonunion of nonoperatively treated clavicle fractures? METHODS: In this secondary retrospective analysis of an earlier randomized trial, we studied prospectively collected data from 64 nonoperatively treated patients aged 18 years to 60 years. In the original randomized trial, we compared operative and nonoperative treatment of displaced midshaft clavicular fractures. In all, 150 patients were included in the study, of whom 71 received nonoperative treatment. Patients were predominantly males (75%, 48 of 64) with a mean age of 38 ± SD 12 years; most fractures were comminuted and shortened more than 1 cm. All 71 patients who were nonoperatively treated were potentially eligible for this secondary analysis; of those, 11% (8 of 71) were lost to follow-up, leaving 63 patients from the nonoperative treatment arm and one patient from the operative treatment arm (who declined surgical treatment after randomization but was followed in this group according to the intention-to-treat principle) for analysis here. Nonunion was defined as lack of callus formation, persistent fracture lines and/or sclerotic edges of the bones at the fracture site on plain radiographs at 6 months follow-up. Nonunions were regarded as symptomatic if pain, tenderness, and local crepitation were present at the fracture site. Seventeen percent (11 of 64) of patients had symptomatic nonunions. After investigating differences in early pain scores between the union and nonunion groups, we defined the VASratio as the VAS pain score at 4 weeks divided by the VAS pain score at 2 weeks. Week 2 VAS pain score was chosen as baseline after visual inspection of a linear mixed model that showed increased divergence in pain scores between union and nonunion group at 2 weeks after fracture. Week 4 was chosen as the cutoff because we wanted a reasonable time frame for the detection of pain reduction and did not want to delay surgical treatment more than necessary. Odds ratios for various risk factors were calculated using logistic regression analyses. We used a receiver operating characteristic curve analysis to identify cutoff values for the VASratio. RESULTS: An increase in absolute pain score at 4 weeks after fracture (odds ratio 1.8 per 1 point increase [95% confidence interval 1.1 to 3.4]) was associated with an increased risk of nonunion 6 months after fracture. Likewise, we found that an increasing VASratio (OR 1.02 per 0.01 point increase [95% CI 1.002 to 1.06]) was also associated with nonunion. Receiver operating curve analysis found that the best cutoff value of VASratio was about 0.6. Patients with a VASratio above 0.6 had a relative risk of developing nonunion of 18 (95% CI 2 to 130) compared with patients with a VASratio below 0.6. Sparse-data bias could be present, as is evident from this wide confidence interval, though even at the low end of the confidence interval, the relative risk was 2, which may still improve surgical decision-making. CONCLUSION: A pain score that exhibits no or minimal change from 2 to 4 weeks after nonoperative treatment of a displaced midshaft fracture of the clavicle is associated with a high risk that symptomatic nonunion will develop. Patients with no or minimal change in pain in the early weeks may be candidates for surgery to reduce the risk of symptomatic nonunion. As this was a retrospective study, with a risk of sparse-data bias, the predictive value of the VASratio needs to be further investigated in large prospective studies before clinical use. LEVEL OF EVIDENCE: Level III, diagnostic study.

Wrist function recovery course in patients with scaphoid nonunion treated with combined volar bone grafting and a dorsal antegrade headless screw.

BACKGROUND: Surgical treatment is necessary for scaphoid nonunion. Open surgery with a combined volar and dorsal approach is thought to have poor functional outcomes and a prolonged recovery course. However, the detailed recovery course for this approach is rarely reported. The aim of this study was to investigate the recovery course and radiographic outcome for patients with scaphoid nonunion who underwent a combined volar bone grafting and dorsal antegrade headless screw approach. MATERIAL AND METHODS: Eighteen patients with scaphoid nonunion who underwent combined volar bone grafting and dorsal antegrade headless screw fixation were enrolled in this retrospective study. Preoperative and serial postoperative wrist functional and radiographic outcomes were collected and analysed. RESULTS: All 18 patients achieved bone union at a mean time of 14.3 weeks. Compared to the preoperative status, the grip strength, wrist motion arc, and Mayo Wrist score were improved significantly 6 months after surgery, whilst the Disabilities of the Arm, Shoulder, and Hand (DASH) score did not recover until 12 months after surgery. Significant improvements were found in all scaphoid radiographic parameters. CONCLUSION: The surgical outcomes for scaphoid nonunion treated with a combined volar bone grafting and dorsal antegrade headless screw achieved a high union rate, with great wrist functional and radiographic outcomes. The earliest recovered wrist functional parameters were grip strength, motion arc, Mayo Wrist score and finally the DASH score at postoperative 6 months and 12 months, respectively.

Painful Snapping of Thumb Caused by a Displaced Non-Union Fragment from the Trapezium: A Case Report.

There are only a few reports regarding snapping thumb caused by the pathology of the extensor tendon. We report a rare case of snapping thumb caused by a displaced non-union fragment from the trapezium in a 54-year-old man treated with the surgical resection. The intraoperative findings and the outcome are described.

Complex Monteggia Fractures in the Adult Cohort: Injury and Management.

Monteggia fractures involve proximal ulna fracture associated with a radiocapitellar joint dislocation. The Bado classification is primarily based on the direction of the radial head dislocation. The Jupiter subtype classification of Bado II fractures further characterizes the severity of proximal ulna comminution and the involvement of the coronoid fragment. This latter classification can better prognosticate the challenges of surgical reconstruction and clinical outcomes. Surgery for all adult Monteggia fractures is required to restore the anatomic alignment of the ulna, which indirectly reduces the radiocapitellar joint. The complexity of the injury is considerably increased by comminution of the proximal ulna, the degree of radial head fragmentation, the reduction of the radial head, and ulnohumeral instability. Anatomic reduction is considered critical to achieving a favorable outcome.

Epidemiology, Clinical Assessments, and Current Treatments of Nonunions.

PURPOSE OF REVIEW: The failure of bony union following a fracture, termed a fracture nonunion, has severe patient morbidity and economic consequences. This review describes current consensuses and future directions of investigation for determining why, detecting when, and effective treatment if this complication occurs. RECENT FINDINGS: Current nonunion investigation is emphasizing an expanded understanding of the biology of healing. This has led to assessments of the immune environment, multiple cytokines and morphogenetic factors, and the role of skeletogenic stem cells in the development of nonunion. Detecting biological markers and other objective diagnostic criteria is also a current objective of nonunion research. Treatment approaches in the near future will likely be dominated by the development of specific adjunct therapies to the nonunion surgical management, which will be informed by an expanded mechanistic understanding of nonunion biology. Current consensus among orthopedists is that improved diagnosis and treatment of nonunion hinges first on discoveries at the bench side with later translation to the clinic.

J-bone graft with double locking plate: a symphony of mechanics and biology for atrophic distal femoral non-union with bone defect.

OBJECTIVE: Atrophic distal femur non-union with bone defect (ADFNBD) has been a worldwide challenge to treat due to the associated biological and mechanical problems. The purpose of this study was to introduce a new solution involving the use of a J-shaped iliac crest bone graft (J-bone) combined with double-plate (DP) in the treatment of femoral non-union. METHODS: Clinically, 18 patients with ADFNBD were included in this retrospective study and were treated with a combination of J-bone graft and DP. The average follow-up time was 22.1 ± 5.5 months (range, 14 to 34 months). The imaging information and knee joint activity tests and scores were used to evaluate the time to weight-bearing, the time to non-union healing, and the knee joint mobility. A finite element analysis was used to evaluate the differences between the following: (1) the use of a lateral locking plate (LLP) only group (LLP-only), (2) a DP only group (DP-only), (3) a DP with a J-bone group (DP+J-bone), and (4) an LLP with a J-bone group (LLP+J-bone) in the treatment of ADFNBD. A finite element analysis ABAQUS 6.14 (Dassault systems, USA) was used to simulate the von Mises stress distribution and model displacement of the plate during standing and normal walking. RESULT: All patients with non-union and bone defect in the distal femur achieved bone healing at an average of 22.1 ± 5.5 months (range, 14 to 34 months) postoperatively. The average healing time was 6.72 ± 2.80 months. The knee Lysholm score was significantly improved compared with that before surgery. Under both 750 N and 1800 N axial stress, the maximum stress with the DP+J-bone structure was less than that of the LLP+J-bone and DP-only structures, and the maximum stress of J-bone in the DP+J-bone was significantly less than that of the LLP+J-bone+on structure. The fracture displacement of the DP+J-bone structure was also smaller than that of the LLP+J-bone and DP-only structures. CONCLUSION: J-bone combined with DP resulted in less maximum stress and less displacement than did a J-bone combined with an LLP or a DP-only graft for the treatment of ADFNBD. This procedure was associated with less surgical trauma, early rehabilitation exercise after surgery, a high bone healing rate, and a satisfactory rate of functional recovery. Therefore, a combination of J-bone and DP is an effective and important choice for the treatment of ADFNBD.

Posttraumatic Malunion Following Comminuted Scapular Fracture.

A 42-year-old male police officer sustained multiple injuries in a motorcycle accident, including a comminuted fracture of the scapula and several rib fractures. Four months after his injury, the patient was prescribed outpatient physical therapy, after 2 months of which the patient's cervical and lumbar spine function were restored but his shoulder mobility deficits persisted. A second physical therapy opinion was sought 6 months post injury for the left shoulder. Given his functional deficits, including an inability to return to work, he was referred to an orthopaedist for additional imaging and consultation, which revealed scapular malunion. J Orthop Sports Phys Ther 2020;50(3):167. doi:10.2519/jospt.2020.8927.

Humeral Shaft Fracture Healing Rates in Older Patients.

Nonoperative treatment has become the standard of care for the majority of humeral shaft fractures. Published studies have mainly come from trauma centers with a young cohort of patients. The purpose of this study was to determine the nonunion rate of humeral shaft fractures in patients older than 55 years. A retrospective study was performed on a group of orthopedic trauma group treated at a level I trauma center during a 10-year period (2007-2017). Patients 55 years or older and treated for a humeral shaft fracture nonoperatively, with or without manipulation, were identified. Nonunion was defined by no bridging callus radiographically or by gross motion at the fracture at least 12 weeks from injury. There were 31 patients identified with humeral shaft fractures who met the inclusion criteria. The cohort included 21 (67.7%) females and 10 (32.3%) males with a mean age of 72.5 years (range, 55-92 years). Twenty-one fractures went on to union, and there were 10 nonunions, with no significant differences in the demographics or comorbidities. There was no correlation between AO/OTA fracture classification or fracture location and union status. There was a tendency toward higher risk of nonunion in proximal third humeral shaft fractures (45%) compared with middle (26%) and distal third (20%) humeral shaft fractures, although this was not statistically significant. The overall nonunion rate for humeral shaft fractures was 32% for patients older than 55 years. The authors found a significant correlation between age and union rate: as age increased, union rate decreased (R=-0.9, P=.045). The incidence of humeral shaft nonunion in patients older than 55 years was significantly higher than that of younger adults. To the authors' knowledge, this study is the first to report a significant correlation between nonunion and increased age. [Orthopedics. 2020;43(3);168-172.].

Radiographic evaluations: Which are most effective to follow fracture healing?

The assessment of fracture healing is an imperative and fundamental clinical aspect within orthopaedics. Despite that, there have historically been non-reliable methods utilized to assess for fracture union and nonunion. In recent years, a number of radiographic assessment tools such as the Radiographic Union Score for Tibial fractures (RUST) and Radiographic Union Score for Hip fracture (RUSH) have been developed in order to improve the reliability of fracture assessment for union. These scores have not only increased the reliability of assessments but have also provided thresholds to aid in predicting nonunion as well as union. The nonunion risk determination (NURD) Score was also created to prognosticate these clinical presentations. With the large burdens of cost, lower quality of life and morbidity associated with fracture nonunion, these evaluation methods have provided orthopaedic surgeons with an improved ability to predict nonunion and assist in the management of patients. This review outlines the development, reliability testing as well as biomechanical validity testing associated with these scoring systems.

Outcome of Bone Marrow Injection in Patient with Delayed Union and Non-Uninon of Long Bone Fracture.

Bone marrow is a source of osteoprogenitor cells which are the most important factor of bone formation and healing of fracture. The aim of the study is to evaluate the outcome of bone marrow injection in the management of delayed union and non-union. This prospective study was performed in the department of Orthopaedics, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from January 2017 to June 2019. In this study 21 patients with delayed union and non-union were treated by bone marrow injection. Bone marrow were aspirated from the anterior or posterior iliac crests then injected percutaneously into the fracture site. Full union was achieved in 15 cases, while failed in the others. No major complications were seen during or after the procedure. It is a safe, easy and a minimally invasive procedure compared to usual open bone graft especially for cases with high risk of anesthesia or risk of infection.

Assessment of body balance of patients treated with the Ilizarov method for tibial nonunion.

PURPOSE: The biomechanics of the musculoskeletal system in patients after tibial nonunion treatment using the Ilizarov method have not yet been fully explored. From the orthopaedic and patient point of view, after the treatment, an assessment should be carried out of the biomechanics of the musculoskeletal system. The aim of this study was to assess the body balance of patients treated with the Ilizarov method for tibial nonunion. METHODS: The research group included 24 individuals with a mean age of 55 years, who were treated for aseptic tibial nonunion with the Ilizarov method. The control group was matched to the study group in terms of gender and age, and consisted of 32 subjects with a mean age of 50.5 years and no significant medical history. This study evaluated the balance of patients with the use of pedobarography. RESULTS: In the control group, a statistically significantly shorter path of centre of gravity was observed. There were no statistical differences between the study and control groups for the field area of the centre of gravity. There were no statistical differences between the study and control groups for the minor axis length or major axis length of the centre of gravity. There was a relationship between the centre of pressure path length and the age of the participants in both the control group and the study group. CONCLUSIONS: Treatment of patients with tibial nonunion with the Ilizarov fixator achieves similar balance to healthy volunteers. In the pedobarographic evaluation, patients treated for tibial nonunion using the Ilizarov method had similar statics of the musculoskeletal system to healthy volunteers.

Hypophosphatasia in Adults: Clinical Spectrum and Its Association With Genetics and Metabolic Substrates.

BACKGROUND: Hypophosphatasia (HPP) is a rare metabolic bone disorder caused by mutations in the alkaline phosphatase (ALPL) gene, and characterized by low circulating alkaline phosphatase (ALP) levels and bone, muscle, dental and systemic manifestations. In this case series we investigate the clinical spectrum, genetic and biochemical profile of adult HPP patients from the University Hospitals Leuven, Belgium. METHODOLOGY: Adults with HPP were identified through medical record review. Inclusion criteria were: (1) age ≥ 16 yr; (2) consecutively low ALP levels not explained by secondary causes; (3) one or more of the following supporting criteria: biochemical evidence of elevated enzyme substrates; subtrochanteric fractures, metatarsal fractures or other typical clinical features; family history of HPP; a known or likely pathogenic ALPL mutation. RESULTS: Nineteen patients met our inclusion criteria (n = 2 infantile, n = 6 childhood, n = 10 adult-onset HPP and one asymptomatic carrier). Fractures and dental abnormalities were the most reported symptoms. Fatigue was reported in n = 7/19 patients (37%), three of which had previously been misdiagnosed as having chronic fatigue syndrome and/or fibromyalgia. Empirical pyridoxine therapy in four patients (without seizures) did not provide symptomatic relief. N = 7/19 patients (37%) were inappropriately treated or planned to be treated with antiresorptive treatment. Two patients developed atypical femoral fractures following exposure to bisphosphonates and/or denosumab. Patients detected by screening were less severely affected, while patients with homozygous or compound heterozygous mutations had the most severe symptoms, significantly lower circulating ALP levels (p = 0.013) and significantly higher pyridoxal-5'-phosphate (p = 0.0018) and urinary phosphoethanolamine (p = 0.0001) concentrations. CONCLUSIONS: Screening may detect mainly less severely affected individuals, which may nevertheless avoid misdiagnosis and inappropriate antiresorptive drug exposure. Patients with biallelic mutations had more severe symptoms, significantly lower ALP and higher substrate levels. Whether the latter finding has implications for the classification and treatment of HPP should be investigated further in larger cohorts.

Does the induced membrane have antibacterial properties? An experimental rat model of a chronic infected nonunion.

INTRODUCTION: The Masquelet procedure proved its efficiency in treating infected nonunion filling bony gaps up to 25 cm. Yet the use of local antibiotics is still questionable in the daily practice with lack of evidence regarding its usefulness in controlling infection. An experimental rat model is put in place to study the antibacterial properties of the induced membrane produced during the first stage of Masquelet. METHOD: Twenty-three-month-old wistar male rats are inoculated with a 0.5 mL solution of 10^8 CFU/mL MRSA over a critical fracture done on the right femur. Six weeks later, remaining 11 rats exhibiting signs of a chronic infection with a sinus tract and oozing pus along with radiological nonunion are used for a first stage Masquelet procedure. They are randomly divided into two groups with six rats having no local antibiotic in the cement mixture and five rats having 3 g of vancomycin mixed with gentamycin loaded cement. Six weeks later (twelve weeks from baseline), all eleven rats are euthanized and blood samples for C-reactive protein are withdrawn. The induced membrane is identified and resected along with bone fragments and sent for cultures and pathology. RESULTS: MRSA is isolated in the cultures of all six rats in the first group where no local antibiotic was added. Altered polymorphonuclears with abscess and pus are noted on four of six pathology samples. However in the second group where local antibiotics were added, three out of five rats exhibited eradication of MRSA (p = 0.034) and all samples did not exhibit clear infection signs on pathology. A pyo-epithelioid over a foreign body reaction is seen predominantly in this group demonstrating a regenerative process. DISCUSSION: The induced membrane does not have antimicrobial properties capable of overcoming an infected nonunion on its own. When local antibiotics were added during the first stage of the Masquelet procedure, new bone formation occurred indicating the need to control an infection in order for bone union to occur. CONCLUSION: Local antibiotics use in adjunction to extensive debridement is advisable during the first stage of a Masquelet procedure for an infected nonunion.