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Purpose The primary objective of this study was to quantify the variations of the medial posterior tibial slope (MPTS) and the lateral posterior tibial slope (LPTS), as well as of the medial proximal tibial angle (MPTA), and to determine the fraction of patients for which standard techniques including different alignment techniques would result in alteration of the patient’s individual posterior tibial slope (PTS) and MPTA. Furthermore, it was of interest if a positive correlation between PTS and MPTA or between medial and lateral slope exists. Methods A retrospective study was performed on CT-scans of 234 consecutively selected European patients undergoing individual total knee replacement. All measurements were done on three-dimensional CAD models, which were generated on the basis of individual CT-scans, including the hip, knee, and ankle center. Measurements included the medial and lateral PTS and the MPTA. PTS was measured as the angle between the patient’s articular surface and a plane perpendicular to the mechanical axis of the tibia in the sagittal plane. MPTA was defined as the angle between the tibial mechanical axis and the proximal articular surface of the tibia in the coronal plane. Results Analysis revealed a wide variation of the MPTS, LPTS, and MPTA among the patients. MPTS and LPTS varied significantly both interindividually and intraindividually. The range of PTS was up to 20° for MPTS (from − 4.3° to 16.8°) and for LPTS (from − 2.9 to 17.2°). The mean intraindividual difference between MPTS and LPTS in the same knee was 2.6° (SD 2.0) with a maximum of 9.5°. MPTA ranged from 79.8 to 92.1° with a mean of 86.6° (SD ± 2.4). Statistical analysis revealed a weak positive correlation between MPTA and MPTS. Conclusion The study demonstrates a huge interindividual variability in PTS and MPTA as well as significant intraindividual differences in MPTS and LPTS. Therefore, the question arises, whether the use of standard techniques, including fixed PTSs and MPTAs, is sufficient to address every single patient’s individual anatomy. Level of evidence III.

Background During lower limb lengthening, poor bone regeneration is a devastating complication. Several local or systemic applications have been used to promote osteogenesis, and biologic stimulations are gaining attention, but their utility has not been proven in this setting. Questions/purposes In patients undergoing bilateral tibial lengthening, we compared those receiving an osteotomy site injection of autologous bone marrow aspirate concentrate (BMAC) plus platelet-rich plasma (PRP) with those not receiving such an injection in terms of external fixator index (time in external fixation divided by amount of lengthening), full weightbearing index (time until a patient was permitted to do full weightbearing divided by amount of lengthening), four cortical healing indexes (time until each cortical union divided by amount of lengthening), and callus shape and type. Methods Twenty-two patients (44 tibias) undergoing bilateral tibial lengthening enrolled in this randomized trial. Two patients were excluded, one due to insufficient radiographic evaluation and one who was lost to followup, leaving 20 patients (40 segments) for inclusion. Ten patients (20 segments) received BMAC combined with PRP injection (treatment group) and 10 patients (20 segments) received no injection (control group). All patients underwent stature lengthening for familial short stature with the lengthening over nail technique. Autologous BMAC combined with PRP was injected at the tibial osteotomy site at the end of the index surgery. Mean distraction rates were similar between groups (0.75 mm/day in the treatment group versus 0.72 mm/day in the control group; p = 0.24). Full weightbearing was permitted when we observed radiographic evidence of healing at two cortices; this assessment was made by the surgeon who was blinded to the treatment each patient received. Minimum followup was 24 months (mean, 28 months; range, 24–34 months). Results There was no difference in mean external fixator index between groups. However, mean cortical healing indexes (anterior/posterior/medial/lateral) were 1.14/0.81/0.96/0.88 months/cm in the treatment group and 1.47/1.26/1.42/1.22 months/cm in the control group (all p < 0.001), showing faster healing in the treatment group at each cortex. Full weightbearing was permitted earlier in the treatment group than in the control group (index: 0.99 months/cm and 1.38 months/cm, respectively, p < 0.001). Callus shape and type were not different between groups. Conclusions Autologous BMAC combined with PRP injection at the osteotomy site helped improve bone healing in distraction osteogenesis of the tibia, although the effect size was small. Level of Evidence Level I, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Purpose This study aimed to compare the difference in posterior tibial slope (PTS) measurements based on the full-length and half-length tibial anatomic axes of the same group of patients. It was hypothesized that the obtained PTS values would be affected by the length of tibia chosen during the measurements. Methods Full-length true lateral tibia radiographs were obtained for each patient who underwent anterior cruciate ligament reconstruction (ACLR) in our department. PTS measurements were obtained by measuring the angle between the full-length or half-length tibial anatomic axis and an average of the lateral and medial tibial plateau. The anatomic axis was defined as the center of the tibial diaphysis. The PTS measurements from the full-length and half-length true lateral tibia radiographs were obtained and compared. Additionally, the absolute difference and the relationship between the two PTS measurements were calculated and analyzed. Results A total of 200 ACL-injured patients were included in this study. The average PTS values using the anatomic axis were 15.9 ± 3.7° and 14.1 ± 3.7° on full-length and half-length true lateral tibial radiographs. There was a significant difference between the measurements with the full-length and half-length tibial radiographs ( P  < 0.01). Additionally, 49.5% ( n  = 99) of patients had ≥ 2.0° differences between the full-length and half-length anatomic axis PTS measurement techniques; meanwhile, a strong and significant linear relationship ( r  = 0.95; P  < 0.001) was identified between the two PTS measurements. Conclusion There were significant differences and linear relationships between PTS measurements that measured the anatomic axis from full-length and half-length true lateral tibia radiographs. Therefore, the obtained PTS values were strongly associated with the length of tibia chosen during the measurements. Surgeons should pay more attention to the measurement techniques and the tibial length when considering the role of PTS in ACL injury and ACLR failure. Knowledge of the association is very important for calculating potential closing wedge proximal tibial osteotomies to correct excessive PTS in the setting of ACLR failures. Level of evidence IV.

Background Previous designs of internal bone lengthening devices have been fraught with imprecise distraction, resulting in nerve injuries, joint contractures, nonunions, and other complications. Recently, a magnet-operated PRECICE ® nail (Ellipse Technologies, Inc, Irvine, CA, USA) was approved by the FDA; however, its clinical efficacy is unknown. Questions/purposes We evaluated this nail in terms of (1) accuracy and precision of distraction, (2) effects on bone alignment, (3) effects on adjacent-joint ROM, and (4) frequency of implant-related and non-implant-related complications. Methods We reviewed medical and radiographic records of 24 patients who underwent femoral and/or tibial lengthening procedures using the PRECICE ® nail from August 2012 to July 2013 for conditions of varied etiology, the most common being congenital limb length discrepancy, posttraumatic growth arrest, and fracture malunion. This group represented 29% of patients (24 of 82) who underwent a limb lengthening procedure for a similar diagnosis during the review period. At each postoperative visit, the accuracy and precision of distraction, bone alignment, joint ROM, and any complications were recorded by the senior surgeon (SRR). Accuracy reflected how close the measured lengthening was to the prescribed distraction at each postoperative visit, while precision reflected how close the repeated measurements were to each other over the course of total lengthening period. No patients were lost to followup. Minimum followup from surgery was 3 weeks (mean, 14 weeks; range, 3–29 weeks). Results Mean total lengthening was 35 mm (range, 14–65 mm), with an accuracy of 96% and precision of 86%. All patients achieved target lengthening with minimal unintentional effects on bone alignment. The knee and ankle ROM were minimally affected. Of the complications requiring return to the operating room for an additional surgical procedure, there was one (4%) implant failure caused by a nonfunctional distraction mechanism and six (24%) non-implant-related complications, including premature consolidation in one patient (4%), delayed bone healing in two (8%), delayed equinus contracture in two (8%), and toe clawing in one (4%). Conclusions We conclude that this internal lengthening nail is a valid option to achieve accurate and precise limb lengthening to treat a variety of conditions with limb shortening or length discrepancy. Randomized, larger-sample, long-term studies are required to further confirm clinical efficacy of these devices, monitor for any late failures and complications, and compare with other internal lengthening devices with different mechanisms of operation. Level of Evidence Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Rotational deformities following intramedullary (IM) nailing of tibia has a reported incidence of as high as 20%. Common techniques to measure deformities following IM nailing of tibia are either based on clinical assessment, plain X-rays or Computed Tomography (CT) comparing the treated leg with the uninjured contralateral side. All these techniques are based on examiners manual calculation inherently subject to bias. Following our previous rigorous motion analysis and symmetry studies on hemi pelvises, femurs and orthopaedic implants, we aimed to introduce a novel fully digital technique to measure rotational deformities in the lower legs. Following formal institutional approval from the Imperial College, CT images of 10 pairs of human lower legs were retrieved. Images were anonymized and uploaded to a research server. Three dimensional CT images of the lower legs were bilaterally reconstructed. CT-based motion analysis (CTMA) was used and the mirrored images of the left side were merged with the right side proximally as stationary and distally as moving objects. Discrepancies in translation and rotation were automatically calculated. Our study population had a mean age of 54 ± 20 years. There were six males and four females. We observed a greater variation in translation (mm) of Centre of Mass (COM) in sagittal plane (95% CI − 2.959–.292) which was also presented as rotational difference alongside the antero-posterior direction or Y axis (95% CI .370–1.035). In other word the right lower legs in our study were more likely to be in varus compared to the left side. However, there were no statistically significant differences in coronal or axial planes. Using our proposed fully digital technique we found that lower legs of the human adults were symmetrical in axial and coronal plane. We found sagittal plane differences which need further addressing in future using bigger sample size. Our novel recommended technique is fully digital and commercially available. This new technique can be useful in clinical practice addressing rotational deformities following orthopaedic surgical intervention. This new technique can substitute the previously introduced techniques.

Vitamin D is important for normal skeletal homeostasis, especially in growing children. There are no previous genome-wide association (GWA) studies exploring genetic factors that influence vitamin D metabolism in early childhood. We performed a GWA study on serum 25-hydroxyvitamin D (25(OH)D) and response to supplementation in 761 healthy term-born Finnish 24-month-old children, who participated in a randomized clinical trial comparing effects of 10 μg and 30 μg of daily vitamin D supplementation from age 2 weeks to 24 months. Using the Illumina Infinium Global Screening Array, which has been optimized for imputation, a total of 686085 markers were genotyped across the genome. Serum 25(OH)D was measured at the end of the intervention at 24 months of age. Skeletal parameters reflecting bone strength were determined at the distal tibia at 24 months using peripheral quantitative computed tomography (pQCT) (data available for 648 children). For 25(OH)D, two strong GWA signals were identified, localizing to GC (Vitamin D binding protein) and CYP2R1 (Vitamin D 25-hydroxylase) genes. The GWA locus comprising the GC gene also associated with response to supplementation. Further evidence for the importance of these two genes was obtained by comparing association signals to gene expression data from the Genotype-Tissue Expression project and performing colocalization analyses. Through the identification of haplotypes associated with low or high 25(OH)D concentrations we used a Mendelian randomization approach to show that haplotypes associating with low 25(OH)D were also associated with low pQCT parameters in the 24-month-old children. In this first GWA study on 25(OH)D in this age group we show that already at the age of 24 months genetic variation influences 25(OH)D concentrations and determines response to supplementation, with genome-wide significant associations with GC and CYP2R1. Also, the dual association between haplotypes, 25(OH)D and pQCT parameters gives support for vertical pleiotropy mediated by 25(OH)D.

Background Key factors limiting patients with lower extremity amputations to achieve maximal functional capabilities are falls and fear of falling. A task-specific fall prevention training program has successfully reduced prospectively recorded trip-related falls that occur in the community by the elderly. However, this program has not been tested in amputees. Questions/purposes In a cohort of unilateral transtibial amputees, we aimed to assess effectiveness of a falls prevention training program by (1) quantifying improvements in trunk control; (2) measuring responses to a standardized perturbation; and (3) demonstrating retention at 3 and 6 months after training. Second, we collected patient-reported outcomes for balance confidence and falls control. Methods Fourteen male military service members (26 ± 3 years) with unilateral transtibial amputations and who had been walking without an assistive device for a median of 10 months (range, 2–106 months) were recruited to participate in this prospective cohort study. The training program used a microprocessor-controlled treadmill designed to deliver task-specific postural perturbations that simulated a trip. The training consisted of six 30-minute sessions delivered over a 2-week period, during which task difficulty, including perturbation magnitude, increased as the patient’s ability progressed. Training effectiveness was assessed using a perturbation test in an immersive virtual environment. The key outcome variables were peak trunk flexion and velocity, because trunk kinematics at the recovery step have been shown to be a determinant of fall likelihood. The patient-reported outcomes were also collected using questionnaires. The effectiveness of the rehabilitation program was also assessed by collecting data before perturbation training and comparing the key outcome parameters with those measured immediately after perturbation training (0 months) as well as both 3 and 6 months posttraining. Results Mean trunk flexion angle and velocity significantly improved after participating in the training program. The prosthetic limb trunk flexion angle improved from pretraining (42°; 95% confidence interval [CI], 38°–47°) to after training (31°; 95% CI, 25°–37°; p < 0.001). Likewise, the trunk flexion velocity improved from pretraining (187°/sec; 95% CI, 166°–209°) to after training (143°/sec; 95% CI, 119°–167°; p < 0.004). The results display a significant side-to-side difference for peak trunk flexion angle (p = 0.01) with perturbations of the prosthetic limb resulting in higher peak angles. Prosthetic limb trips also exhibited significantly greater peak trunk flexion velocity compared with trips of the prosthetic limb (p = 0.005). These changes were maintained up to 6 months after the training. The peak trunk flexion angle of the subjects when the prosthetic limb was perturbed had a mean of 31° (95% CI, 25°–37°) at 0 month, 32° (95% CI, 28°–37°) at 3 months, and 30° (95% CI, 25°–34°) at 6 months. Likewise, the peak trunk flexion velocity for the prosthetic limb was a mean of 143°/sec (95% CI, 118°–167°) at 0 months, 143°/sec (95% CI, 126°–159°) at 3 months, and 132° (95% CI, 115°–149°) at 6 months. The peak trunk flexion angle when the nonprosthetic limb was perturbed had a mean of 22° (95% CI, 18°–24°) at 0 months, a mean of 26° (95% CI, 20°–32°) at 3 months, and a mean of 23° (95% CI, 19°–28°) at 6 months. The peak trunk flexion velocity for the nonprosthetic limb had a mean of 85°/sec (95% CI, 71°–98°) at 0 months, a mean of 96° (95% CI, 68°–124°) at 3 months, and 87°/sec (95% CI, 68°–105°) at 6 months. There were no significant changes in the peak trunk flexion angle (p = 0.16) or peak trunk flexion velocity (p = 0.35) over time after the training ended. The skill retention was present when either the prosthetic or nonprosthetic limb was perturbed. There were side-to-side differences in the trunk flexion angle (p = 0.038) and trunk flexion velocity (p = 0.004). Perturbations of the prosthetic side resulted in larger trunk flexion and higher trunk flexion velocities. Subjects prospectively reported decreased stumbles, semicontrolled falls, and uncontrolled falls. Conclusions These results indicate that task-specific fall prevention training is an effective rehabilitation method to reduce falls in persons with lower extremity transtibial amputations. Level of Evidence Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

The bone marrow adjusts blood cell production to meet physiological demands in response to insults. The spatial organization of normal and stress responses are unknown owing to the lack of methods to visualize most steps of blood production. Here we develop strategies to image multipotent haematopoiesis, erythropoiesis and lymphopoiesis in mice. We combine these with imaging of myelopoiesis 1 to define the anatomy of normal and stress haematopoiesis. In the steady state, across the skeleton, single stem cells and multipotent progenitors distribute through the marrow enriched near megakaryocytes. Lineage-committed progenitors are recruited to blood vessels, where they contribute to lineage-specific microanatomical structures composed of progenitors and immature cells, which function as the production sites for each major blood lineage. This overall anatomy is resilient to insults, as it was maintained after haemorrhage, systemic bacterial infection and granulocyte colony-stimulating factor (G-CSF) treatment, and during ageing. Production sites enable haematopoietic plasticity as they differentially and selectively modulate their numbers and output in response to insults. We found that stress responses are variable across the skeleton: the tibia and the sternum respond in opposite ways to G-CSF, and the skull does not increase erythropoiesis after haemorrhage. Our studies enable in situ analyses of haematopoiesis, define the anatomy of normal and stress responses, identify discrete microanatomical production sites that confer plasticity to haematopoiesis, and uncover unprecedented heterogeneity of stress responses across the skeleton. This study develops a method for spatially resolving multipotent haematopoiesis, erythropoiesis and lymphopoiesis in mice and uncovers heterogeneous haematopoietic stress responses in different bones.

Purpose The currently used system to classify the lower limb alignment (neutral, varus, valgus) does not consider the orientation of the joint line or its relationship to the overall lower limb alignment. Similarly, current total knee arthroplasty (TKA) alignment concepts do not sufficiently consider the variability of the native coronal alignment. Therefore, the purpose of this study was (1) to introduce a new classification system for the lower limb alignment, based on phenotypes, and (2) to compare the alignment targets of different TKA alignment concepts with the native alignment of non-osteoarthritic patients. Methods Two recent articles phenotyped the lower limb, the femur and tibia of 308 non-osteoarthritic knees of 160 patients [male to female ratio = 102:58, mean age ± standard deviation 30 ± 7 years (16–44 years)]. The present study introduces functional knee phenotypes, which are a combination of all previously introduced phenotypes. The functional knee phenotypes therefore enable an evaluation of all parameters in relation to each other and thus a comprehensive analysis of the coronal alignment. The existing functional knee phenotypes in the female and male population were investigated. In addition, how many non-osteoarthritic knees had an alignment within the range of current TKA alignment targets (mechanical, anatomical and restricted kinematic alignment) was investigated. Therefore, it was defined which functional knee phenotypes represented a target of the TKA alignment concepts and which percentage of the population had such a phenotype. Results Out of 125 possible functional knee phenotypes, 43 were found (35 male, 26 and 18 mutual). The most common functional knee phenotype in males was NEU HKA 0° + NEU FMA 0° + NEU TMA 0° (19%), followed by VAR HKA 3° + NEU FMA 0° + VAR TMA 0° (8.2%). The most common functional knee phenotype in females was NEU HKA 0° + NEU FMA 0° + NEU TMA 0° (17.7%), closely followed by NEU HKA 0° + NEU FMA 0° + VAL TMA 0° (16.6%). The functional knee phenotype representing a mechanical alignment target was found in 5.6% of the males and 3.6% of the females. The phenotype representing an anatomical alignment target was found in 18% of the males and 17% in females. Five of the nine phenotypes representing a restricted kinematic alignment target were found in this population (male 5, female 4, mutual 4). They represented 31.3% of all males and 45.1% of all females. Conclusion A more individualized approach to TKA alignment is needed. The functional knee phenotypes enable a simple, but detailed assessment of a patient’s individual anatomy and thereby could be a helpful tool to individualize the approach to TKA. Level of clinical evidence III, retrospective cohort study.

Innate immune cells recruited to inflammatory sites have short life spans and originate from the marrow, which is distributed throughout the long and flat bones. While bone marrow production and release of leukocyte increases after stroke, it is currently unknown whether its activity rises homogeneously throughout the entire hematopoietic system. To address this question, we employed spectrally resolved in vivo cell labeling in the murine skull and tibia. We show that in murine models of stroke and aseptic meningitis, skull bone marrow-derived neutrophils are more likely to migrate to the adjacent brain tissue than cells that reside in the tibia. Confocal microscopy of the skull–dura interface revealed myeloid cell migration through microscopic vascular channels crossing the inner skull cortex. These observations point to a direct local interaction between the brain and the skull bone marrow through the meninges.