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Abstract Background Bone repair is dependent on the presence of osteocompetent progenitors that are able to differentiate and generate new bone. Muscle is found in close association with orthopaedic injury, however its capacity to make a cellular contribution to bone repair remains ambiguous. We hypothesized that myogenic cells of the MyoD-lineage are able to contribute to bone repair. Methods We employed a MyoD-Cre+:Z/AP+ conditional reporter mouse in which all cells of the MyoD-lineage are permanently labeled with a human alkaline phosphatase (hAP) reporter. We tracked the contribution of MyoD-lineage cells in mouse models of tibial bone healing. Results In the absence of musculoskeletal trauma, MyoD-expressing cells are limited to skeletal muscle and the presence of reporter-positive cells in non-muscle tissues is negligible. In a closed tibial fracture model, there was no significant contribution of hAP+ cells to the healing callus. In contrast, open tibial fractures featuring periosteal stripping and muscle fenestration had up to 50% of hAP+ cells detected in the open fracture callus. At early stages of repair, many hAP+ cells exhibited a chondrocyte morphology, with lesser numbers of osteoblast-like hAP+ cells present at the later stages. Serial sections stained for hAP and type II and type I collagen showed that MyoD-lineage cells were surrounded by cartilaginous or bony matrix, suggestive of a functional role in the repair process. To exclude the prospect that osteoprogenitors spontaneously express MyoD during bone repair, we created a metaphyseal drill hole defect in the tibia. No hAP+ staining was observed in this model suggesting that the expression of MyoD is not a normal event for endogenous osteoprogenitors. Conclusions These data document for the first time that muscle cells can play a significant secondary role in bone repair and this knowledge may lead to important translational applications in orthopaedic surgery. Please see related article: http://www.biomedcentral.com/1741-7015/9/136

Background: Hip dysplasia is a lack of femoral head coverage and disruption of hip and acetabular alignment and congruency, with severity ranging from mild subluxation in nascent at-risk hips to complete dislocation. Presentation of hip dysplasia in neuromuscular conditions can be sub-clinical or associated with a limp with or without hip pain, abductor and flexor weakness and reduced hip range of motion. Untreated hip dysplasia leads to early onset osteoarthritis requiring hip arthroplasty in early adulthood. Hip dysplasia occurs in 6-20% of children with Charcot-Marie-Tooth disease, however little is known about the reliability and sensitivity of detection on plain film pelvic radiographs., Methods: 14 common measures of hip dysplasia on anteroposterior pelvis radiographs were independently assessed by 2 orthopaedic specialists in 30 ambulant children with Charcot-Marie-Tooth disease. Hip health was also categorised based on clinical impression to assess the sensitivity of radiographic measures to identify hip dysplasia status., Results: 8 measures (acetabular index, head width, lateral centre-edge angle, lateral uncoverage, medial joint width, migration percentage, neck shaft angle, triradiate status) exhibited 'excellent' reliability between clinical evaluators. 5 of the 30 patients (17%) were identified as having nascent hip dysplasia. Reliable radiographic measures that significantly distinguished between nascent hip dysplasia and healthy hips were acetabular index, lateral centre edge angle, medial joint width and migration percentage., Conclusions: We have identified a subset of reliable and sensitive radiographic hip measures in children with Charcot-Marie-Tooth disease to prioritise during hip screening to mitigate the deleterious effects of hip dysplasia, pain and disability in adulthood.

Purpose: Longitudinal fibular deficiency (LFD) is the most common congenital long bone deficiency. This study aimed to objectively assess the physical performance of children and adolescents with LFD compared with unaffected peers, and to examine trends over age for subgroups of the LFD population., Methods: Differences between children with LFD and unaffected peers were examined with hand-held dynamometry for lower-limb muscle strength, Six-Minute Walk Test, Timed up and down stairs test, Star Excursion Balance Test, and Standing long jump., Results: Thirty-nine children with LFD and 284 unaffected peers participated. Children with LFD performed at a lower level than their unaffected peers, on all measures of physical performance (mean 2.1 z -scores lower, all p  < 0.01), except in long jump ( p  = 0.27). When comparing the performance of children with LFD to their unaffected peers across four age groups, there was a significant between-groups difference on all strength measures, and on the Six-Minute Walk distance, between children with and without LFD. These differences were smallest in young children (3-6 years) and largest in the older children (15-18 years) (all p  < 0.01). Children with no lengthening surgery performed better on the Six-Minute Walk Test, covering a greater distance during the test, than those who had surgery (mean difference 83 metres, p  < 0.01). There were no significant differences between children who had or had not undergone an amputation., Conclusions: Children with LFD performed at a significantly lower level than unaffected peers on all measures of physical performance other than jumping. The largest differences were in older children. This paper provides baseline functional data for future interventions in LFD., Level of Evidence: Cross-sectional study.Implications for RehabilitationThis paper provides the first baseline functional data using validated objective measures on a consecutive cohort of children and adolescents with longitudinal fibular deficiency.Children with LFD performed significantly worse than their unaffected peers on all measures of physical performance other than jumping, with children falling further behind their peers as they age.Children who undergo an amputation typically have the most severe anatomical presentation and yet perform at an equivalent functional level.This paper identifies multiple modifiable impairments that represent potential opportunities for rehabilitation professionals to target with conservative treatment options to improve functional performance.

Purpose: The modified Dunn procedure for slipped capital femoral epiphysis (SCFE) remains controversial. We reviewed our series over ten years to report our learning curve, experience with intraoperative monitoring of femoral head perfusion and its correlation with postoperative Single-photon emission computed tomography (SPECT-CT) bone scan and femoral head collapse in stable and unstable SCFE., Methods: We retrospectively assessed 217 consecutive modified Dunn procedures performed between 2008 and 2018. In all, 178 had a minimum of one-year follow-up (mean 2.7 years (1 to 9.2)) including 107 stable and 71 unstable SCFE. Postoperative viability was assessed with a three-phase Tc99 bone scan and SPECT-CT. From 2011, femoral head perfusion monitoring was performed intraoperatively using a Codman Intracranial Pressure transducer and the capsulotomy was modified., Results: With intraoperative monitoring, the rate of non-viable femoral heads in stable SCFE decreased from 21.1% to 0% (p < 0.001). In unstable SCFE, the rate remained unchanged from 35.7% to 29.8% (p = 0.669). The positive predictive value (PPV) of pulsatile monitoring for no collapse was 100% in stable and 89.1% in unstable SCFE. Pulsatile monitoring and viable SPECT-CT bone scan gave a 100% PPV for all cases. A non-viable scan defines those hips at risk of collapse since 100% of stable and 68.2% of unstable hips with non-viable bone scans went on to collapse., Conclusion: Our protocol enables safe performance of this complex procedure in stable SCFE with intraoperative monitoring being a reliable asset. The avascular necrosis rate for unstable SCFE remained unchanged and further research into its best management is required., Level of Evidence: Level III., (Copyright © 2021, The author(s).)

Aim: Australia utilises a selective ultrasound screening programme. The rate of late diagnosis of developmental dysplasia of the hip (DDH) in Australia is increasing. The aim of this study is to quantify the treatment required and compare the 5-year radiological outcomes between early and late diagnosis in children with DDH with frank dislocation., Methods: We performed a case-matched control study of children with frank DDH dislocations from 2000 to 2010 comparing three groups: children with an early diagnosis successfully treated in a Pavlik harness (SP), children with an early diagnosis who failed Pavlik harness treatment (FP) and children with a late diagnosis (LD). Minimum follow-up was 4 years., Results: A total of 115 hips were included. Patients in the LD group required significantly more open reductions (P < 0.001), acetabular osteotomies (P < 0.001) and femoral osteotomies (P < 0.001). LD was also associated with significantly higher rates of growth disturbance at 46.3%, compared to 20.6% in the FP group and 5% in the SP group (P < 0.001). Overall, there were excellent radiological outcomes in 58.5% of the LD group compared to 79.4% in the FP group and 100% in the SP group., Conclusion: In Australia, high rates of LD in DDH persist in the context of selective ultrasound screening. While good radiological outcomes are achievable, a significantly greater level of surgical intervention is required and this is associated with significantly higher rates of growth disturbance. Optimisation of screening in Australia is vital., (© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Neutralizing monoclonal sclerostin antibodies are effective in promoting bone formation at a systemic level and in orthopedic scenarios including closed fracture repair. In this study we examined the effects of sclerostin antibody (Scl-Ab) treatment on regenerate volume, density, and strength in a rat model of distraction osteogenesis. Surgical osteotomy was performed on 179 Sprague Dawley rats. After 1 week, rats underwent distraction for 2 weeks, followed by 6 weeks for consolidation. Two treatment groups received biweekly subcutaneous Scl-AbIII (a rodent form of Scl-Ab; 25 mg/kg), either from the start of distraction onward or restricted to the consolidation phase. These groups were compared to controls receiving saline. Measurement modalities included longitudinal DXA, ex vivo QCT, and microCT, tissue histology, and biomechanical four-point bending tests. Bone volume was increased in both Scl-Ab treatments regimens by the end of consolidation (+26-38%, p < 0.05), as assessed by microCT. This was associated with increased mineral apposition. Importantly, Scl-Ab led to increased strength in united bones, and this reached statistical significance in animals receiving Scl-Ab during consolidation only (+177%, p < 0.01, maximum load to failure). These data demonstrate that Scl-Ab treatment increases bone formation, leading to regenerates with higher bone volume and improved strength. Our data also suggest that the optimal effects of Scl-Ab treatment are achieved in the latter stages of distraction osteogenesis. These findings support further investigation into the potential clinical application of sclerostin antibody to augment bone distraction, such as limb lengthening, particularly in the prevention of refracture. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1106-1113, 2018., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: The modified Dunn procedure facilitates femoral capital realignment for slipped capital femoral epiphysis (SCFE) through a surgical hip dislocation approach. Iatrogenic postoperative hip instability after this procedure has not been studied previously; however, we were concerned when we observed several instances of this serious complication, and we wished to study it further., Questions/purposes: The purpose of this study was to evaluate the frequency, timing, and clinical presentation (including complications) associated with iatrogenic instability after the modified Dunn procedure for SCFE., Methods: Between 2007 and 2014, eight international institutions performed the modified Dunn procedure through a surgical dislocation approach in 406 patients. During the period in question, indications varied at those sites, but the procedure was used only in a minority of their patients treated surgically for SCFE (31% [406 of 1331]) with the majority treated with in situ fixation. It generally was performed for patients with severe deformity with a slip angle greater than 40°. Institutional databases were searched for all patients with SCFE who developed postoperative hip instability defined as hip subluxation or dislocation of the involved hip during the postoperative period. We reviewed in detail the clinical notes and operative records of those who presented with instability. We obtained demographic information, time from slip to surgery, type of fixation, operative details, and clinical course including the incidence of complications. Followup on those patients with instability was at a mean of 2 years (range, 1-5 years) after the index procedure. Complications were graded according to the modified Dindo-Clavien classification. Radiographic images were reviewed to measure the preoperative slip angle and the presence of osteonecrosis., Results: A total of 4% of patients treated with the modified Dunn procedure developed postoperative hip instability (17 of 406). Mean age of the patients was 13 years (range, 9-16 years). Instability presented as persistent hip pain in the postoperative period or was incidentally identified radiographically during the postoperative visit and occurred at a median of 3 weeks (range, 1 day to 2 months) after the modified Dunn procedure. Eight patients underwent revision surgery to address the postoperative instability. Fourteen of 17 patients developed femoral head avascular necrosis and three of 17 patients underwent THA during this short-term followup., Conclusions: Anterolateral hip instability after the modified Dunn procedure for severe, chronic SCFE is an uncommon yet potentially devastating complication. Future studies might evaluate the effectiveness of maintaining anterior hip precautions for several weeks postoperatively in an abduction brace or broomstick cast to prevent this complication., Level of Evidence: Level IV, therapeutic study.

Background: The posterior sloping angle (PSA) has been shown to be an objective and reproducible predictor of the risk of patients developing contralateral slipped capital femoral epiphysis (SCFE); however, prophylactic fixation remains controversial. This in vitro study investigates the biomechanical basis of using a 15-degree PSA as a threshold for prophylactic fixation., Methods: Synthetic bone in vitro models of the proximal femur were constructed with a PSA of 10 degrees as a control (normal) group (n=6) by performing an osteotomy at the physis and gluing the head back onto the neck. SCFE groups were created with a PSA of 15, 20, 25, 30, 50, or 60 degrees, by excising a wedge from the posterior neck and gluing them back at the new angle with corresponding posterior translation proportional to the slip angle, and loaded superoinferiorly in compression, to failure. Ultimate strength, energy to failure, and stiffness were recorded., Results: Increasing the PSA from 10 to 15 degrees only reduced ultimate strength by 13% (P>0.05; CI, -0.21 to -0.06), though a significantly lesser energy to failure was required (-58%, P<0.05; CI, -0.68 to -0.48). Increasing the angle to 20 degrees resulted in a further significant decrease in strength (-19%, P<0.05; CI, -0.28 to -0.10) and energy to failure (-45%, P<0.05; CI, -0.53 to -0.84). The severe SCFE (60-degree PSA) was significantly weaker and less rigid that the control, and the mild and moderate SCFE models (P<0.01)., Conclusions: These biomechanical data support the threshold of 15-degree PSA as an objective measure for prophylactic fixation of the contralateral hip in SCFE., Clinical Relevance: The number needed to treat with (minimally invasive) prophylactic fixation to prevent contralateral SCFE can be minimized if the above-mentioned threshold is used.

Recent studies suggest a possible role for inhibitors of sclerostin such as sclerostin antibody (Scl-Ab) as an anabolic treatment for osteoporosis. Since Scl-Ab has also been shown to potentiate bone repair, we examined the effect of Scl-Ab treatment in a metaphyseal defect repair model in ovariectomized (OVX) rats. Four weeks after OVX or sham surgery, 3 mm circular defects were created bilaterally in the proximal tibia of all rats. After defect surgery, Saline or 25 mg/kg Scl-Ab was administered twice weekly for 3 weeks. Of note, healing was advanced in the 1-week post-defect surgery in OVX controls over Sham controls, with increases in bone volume and fluorochrome labeling observed. However, by week 2, OVX controls fell significantly behind in the repair response compared with Sham controls. Scl-Ab treatment significantly increased bone volume in the defect in OVX rats over the 3-week time course as examined by either microCT or histology. Significant increases in bone formation via fluorochrome labeling of the new bone were observed with Scl-Ab treatment, while osteoclast parameters were not different. With its powerful anabolic potential, bone-specific activity, and potential for low dosing frequency, Scl-Ab treatment could provide enhanced bone repair, particularly in situations of compromised bone repair such as osteoporotic bone., (Copyright © 2012 Orthopaedic Research Society.)

Background: Allowance for the positional changes of the sciatic nerve is important when considering the safest position of the leg to perform hip operations, specifically the ischial osteotomy during a pelvic triple or periacetabular osteotomy. As for its proximity to the osteotomy site the sciatic nerve can be injured during these operations with the consequence of severe functional impairment. This is the first in-vivo study that demonstrates the effect of hip position upon the location of the sciatic nerve., Methods: We determined how altering the position of the hip moves the nerve toward or away from the infracotyloid groove, the desired starting point of the ischial osteotomy site just inferior to the acetabulum when performing a pelvic triple or periacetabular osteotomy. Magnetic resonance imaging scans of the left hip in 3 different positions (neutral/supine, 30 to 45 degrees flexion, 30 to 45 degrees flexion/abduction/external rotation) were performed in 11 healthy children (5 boys and 6 girls, age 7 to 17 y) without prior hip surgery. The distance between the sciatic nerve and the infracotyloid groove was measured on the magnetic resonance images. Distance ratios based on the neutral position were calculated for flexion and flexion/abduction/external rotation for each of the participants., Results: The sciatic nerve moves toward the ischium osteotomy site in hip flexion without abduction (mean flexion: neutral ratio 0.79, P<0.01). However the nerve moves away from the osteotomy site when the hip is 30 to 45 degrees flexed, abducted, and externally rotated (mean flexion/abduction/external rotation: neutral ratio 1.34), meaning the distance from nerve to infracotyloid groove increases significantly (P<0.01). The mean distances were 14.8 mm (11 to 20 mm) in neutral, 11.8 mm (9 to 16 mm) in flexion, and 20.0 mm (9 to 30 mm) in flexion/abduction/external rotation., Conclusions: The likely safest position of the hip/leg to perform the ischium osteotomy as part of a pelvic triple or periacetabular osteotomy is in flexion, abduction, and external rotation. In this position the osteotomy can be performed via a medial or anterior approach with the nerve the furthest away from the osteotomy site., Level of Evidence: Level II.

Purpose: Congenital pseudarthrosis of the tibia (CPT) is a rare but serious disorder in children. No single approach has clearly emerged as superior in terms of operative procedure, fixation, optimal time for surgery or adjunctive pharmaceutical intervention. CPT is frequently associated with neurofibromatosis type 1 (NF1), a condition featuring deficient bone anabolism and excessive catabolism. We have therefore combined the use of bone morphogenetic proteins (BMP) with bisphosphonates (BP) as an adjunct to surgical intervention., Methods: Between 2002 and 2008 we administered BMP-7 (OP-1) at the time of surgery followed by BP (pamidronate or zoledronic acid) in eight Crawford type IV CPT cases in seven patients (six with a confirmed diagnosis of NF1) with a median age of 7 years (range 2 years 11 months to 12 years) at surgery., Results: In six of eight cases, this approach led to primary healing after a mean of 5.5 months (range 4-7 months). One of these cases represented 17 months after primary healing of a proximal CPT with a new further distal fracture that required multiple operations to finally unite at 19 months. The two remaining cases ultimately reached union after multiple operations at 14 and 30 months, respectively, but required recent treatment for refractures., Conclusion: Based on these clinical data (primary healing in 6/8 cases) and prior pre-clinical findings, we propose that BP therapy may be helpful in preserving the BMP-induced bone formation by inhibiting the osteoclastic bone loss. Key factors to achieve union in CPT include sufficient fixation, meticulous resection of the dysplastic tissue and the establishment of a net anabolic environment for bone healing. Whether our biological concept of balancing the anabolic and catabolic responses with BMP and BP improves healing rates in the complex treatment of NF1 CPT remains uncertain and warrants larger prospective multicentre trials.

In this study we developed novel scaffolds through the controlled substitution and incorporation of strontium and zinc into a calcium-silicon system to form Sr-Hardystonite (Sr-Ca(2)ZnSi(2)O(7), Sr-HT). The physical and biological properties of Sr-HT were compared to Hardystonite (Ca(2)ZnSi(2)O(7)) [HT]. We showed that Sr-HT scaffolds are porous with interconnected porous network (interconnectivity: 99%) and large pore size (300-500 microm) and an overall porosity of 78%, combined with a relatively high compressive strength (2.16+/-0.52 MPa). These properties are essential for enhancing bone ingrowth in load-bearing applications. Sr-HT ceramic scaffolds induced the attachment and differentiation of human bone derived cells (HOB), compared to that for the HT scaffolds. Sr-HT scaffolds enhanced expression of alkaline phosphatase, Runx-2, osteopontin, osteocalcin and bone sialoprotein. The in vivo osteoconductivity of the scaffolds was assessed at 3 and 6 weeks following implantation in tibial bone defects in rats. Histological staining revealed rapid new growth of bone into the pores of the 3D scaffolds with the Sr-HT and HT, relative to the beta-tricalcium phosphate (beta-TCP). In vivo, HT and Sr-HT produced distinct differences in the patterns of degradation of the materials, and their association with TRAP positive osteoclast-like cells with HT appearing more resistant compared to both Sr-HT and beta-TCP., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Under physiological conditions, de-novo synthesis and metabolism of bile acids are confined mainly to the pericentral zone of the liver acinus. In the rat, 3alpha-hydroxy-steroid-dehydrogenase (3alpha-HSD) is the major bile acid-binding protein. At the same time, this protein is involved in the de-novo synthesis and metabolism of bile acids. Because bile acid processing is greater in the pericentral than in the periportal region, we investigated whether 3alpha-HSD is more prevalent in the pericentral than in the periportal area., Design: We determined the 3alpha-HSD-protein and its mRNA in periportal and pericentral rat cells., Method: Rat hepatocytes from the periportal or pericentral areas were isolated using the digitonin perfusion technique. For Northern blotting, a labelled 1.3-kb cDNA insert corresponding to the mRNA sequence of 3alpha-HSD was used. For Western blotting, a polyclonal rabbit antiserum against human 3alpha-HSD was used. Blots were quantified by densitometry using phosphoimaging., Results: The amounts of the 3alpha-HSD-protein and its mRNA were significantly greater in the pericentral than in the periportal cells., Conclusions: The greater occurrence of 3alpha-HSD in pericentral than in periportal hepatocytes is in line with the concept that bile acid synthesis and metabolism take place predominantly in pericentral cells.