Reliability of patellar height indices in children with cerebral palsy and spina bifida.

BACKGROUND: The Koshino (KI) and Caton-Deschamps (CDI) indices are used to measure patellar height in children, with the CDI showing excellent reliability in typically developing (TD) children. Reliability of such measures in children with cerebral palsy (CP) and spina bifida (SB) is unknown. METHODS: Lateral knee radiographs were reviewed retrospectively for children with TD (n = 49), CP (n = 48) and SB (n = 42). Five raters took measurements from radiographs twice, at least two weeks apart. Measurements included the CDI, Insall-Salvati Index (ISI) and KI. Systematic variability (bias) and random variability were examined using repeated measures ANOVA, 95% limits of agreement (LOA) and coefficients of variation (CV). RESULTS: Mean values of all three indices differed among raters (p < 0.0001). A significant difference was seen between the first and second measurements for CDI and KI indicating a learning effect. LOA ranges were large for the CDI (intra-rater: 0.37-0.95, inter-rater: 0.60-1.04) and ISI (intra-rater: 0.25-0.49, inter-rater: 0.51-0.57) for all patient groups. The KI showed a clinically acceptable range for TD participants (intra-rater: 0.14-0.16, inter-rater: 0.11-0.14) with larger ranges for CP (intra-rater: 0.26-0.33, inter-rater 0.0.2-0.35) and SB patients (intra-rater: 0.23-0.27, inter-rater: 0.19-0.25). CVs were lowest (best) for KI (3.8% to 7.4%) and highest (worst) for CDI (14.7% to 23.1%) for all three groups. Results were similar for patients with both open and closed physes. CONCLUSIONS: The KI is the most reliable patellar height measure for paediatric patients with TD, CP and SB, with either open or closed physes. The KI is more complex and experience may be important for valid, reliable measurement.

Vertebral cross-sectional area: an orphan phenotype with potential implications for female spinal health.

A high priority in imaging-based research is the identification of the structural basis that confers greater risk for spinal disorders. New evidence indicates that factors related to sex influence the fetal development of the axial skeleton. Girls are born with smaller vertebral cross-sectional area compared to boys-a sexual dimorphism that is present throughout life and independent of body size. The smaller female vertebra is associated with greater flexibility of the spine that could represent the human adaptation to fetal load. It also likely contributes to the higher prevalence of spinal deformities, such as exaggerated lordosis and progressive scoliosis in adolescent girls when compared to boys, and to the greater susceptibility for spinal osteoporosis and vertebral fractures in elderly women than men.

Early injury to cortical and cancellous bone from induction chemotherapy for adolescents and young adults treated for acute lymphoblastic leukemia.

Diminished bone density and skeletal fractures are common morbidities during and following therapy for acute lymphoblastic leukemia (ALL). While cumulative doses of osteotoxic chemotherapy for ALL have been reported to adversely impact bone density, the timing of onset of this effect as well as other changes to bone structure is not well characterized. We therefore conducted a prospective cohort study in pre-adolescent and adolescent patients (10-21years) newly diagnosed with ALL (n=38) to explore leukemia-related changes to bone at diagnosis and the subsequent impact of the first phase of chemotherapy ("Induction"). Using quantitative computerized tomography (QCT), we found that pre-chemotherapy bone properties were similar to age- and sex-matched controls. Subsequently over the one month Induction period, however, cancellous volumetric bone mineral density (vBMD) decreased markedly (-26.8%, p<0.001) with sparing of cortical vBMD (tibia -0.0%, p=0.860, femur -0.7%, p=0.290). The tibia underwent significant cortical thinning (average cortical thickness-1.2%, p<0.001; cortical area-0.4%, p=0.014), while the femur was less affected. Areal BMD (aBMD) concurrently measured by dual-energy X-ray absorptiometry (DXA) underestimated changes from baseline as compared to vBMD. Biochemical evidence revealed prevalent Vitamin D insufficiency and a net resorptive state at start and end of Induction. Our findings demonstrate for the first time that significant alterations to cancellous and cortical bone develop during the first month of treatment, far earlier during ALL therapy than previously considered. Given that osteotoxic chemotherapy is integral to curative regimens for ALL, these results provide reason to re-evaluate traditional approaches toward chemotherapy-associated bone toxicity and highlight the urgent need for investigation into interventions to mitigate this common adverse effect.

Mechanobiology of soft skeletal tissue differentiation--a computational approach of a fiber-reinforced poroelastic model based on homogeneous and isotropic simplifications.

The material properties of multipotent mesenchymal tissue change dramatically during the differentiation process associated with skeletal regeneration. Using a mechanobiological tissue differentiation concept, and homogeneous and isotropic simplifications of a fiber-reinforced poroelastic model of soft skeletal tissues, we have developed a mathematical approach for describing time-dependent material property changes during the formation of cartilage, fibrocartilage, and fibrous tissue under various loading histories. In this approach, intermittently imposed fluid pressure and tensile strain regulate proteoglycan synthesis and collagen fibrillogenesis, assembly, cross-linking, and alignment to cause changes in tissue permeability (k), compressive aggregate modulus (H(A)), and tensile elastic modulus (E). In our isotropic model, k represents the permeability in the least permeable direction (perpendicular to the fibers) and E represents the tensile elastic modulus in the stiffest direction (parallel to the fibers). Cyclic fluid pressure causes an increase in proteoglycan synthesis, resulting in a decrease in k and increase in H(A) caused by the hydrophilic nature and large size of the aggregating proteoglycans. It further causes a slight increase in E owing to the stiffness added by newly synthesized type II collagen. Tensile strain increases the density, size, alignment, and cross-linking of collagen fibers thereby increasing E while also decreasing k as a result of an increased flow path length. The Poisson's ratio of the solid matrix, nu(s), is assumed to remain constant (near zero) for all soft tissues. Implementing a computer algorithm based on these concepts, we simulate progressive changes in material properties for differentiating tissues. Beginning with initial values of E=0.05 MPa, H(A)=0 MPa, and k=1 x 10(-13) m(4)/Ns for multipotent mesenchymal tissue, we predict final values of E=11 MPa, H(A)=1 MPa, and k=4.8 x 10(-15) m(4)/Ns for articular cartilage, E=339 MPa, H(A)=1 MPa, and k=9.5 x 10(-16) m(4)/Ns for fibrocartilage, and E=1,000 MPa, H(A)=0 MPa, and k=7.5 x 10(-16) m(4)/Ns for fibrous tissue. These final values are consistent with the values reported by other investigators and the time-dependent acquisition of these values is consistent with current knowledge of the differentiation process.

Influence of bone mineral density, age, and strain rate on the failure mode of human Achilles tendons.

OBJECTIVE: To examine the influence of strain rate, bone mineral density, and age in determining the mode by which human Achilles tendons fail. DESIGN: Dual-energy X-ray absorptiometry and mechanical testing of excised Achilles tendon-calcaneus specimens. BACKGROUND: The Achilles tendon can fail by tendon rupture or bony avulsion. These injuries are caused by similar loading mechanisms and can present similar symptoms. It is important to understand when each mode of injury is likely to occur so that accurate diagnoses can be made and appropriate treatments selected. METHODS: Excised human Achilles tendons were loaded to failure at strain rates of 1% s(-1) and 10% s(-1) following dual-energy X-ray absorptiometry examination to determine bone mineral density near the tendon insertion. Calcaneal bone mineral density, donor age, and strain rate were compared between specimens that failed by avulsion and those that failed by tendon rupture. RESULTS: While strain rate was not observed to affect failure mode, the calcaneal bone mineral density of specimens that failed by avulsion was significantly lower than the bone mineral density of specimens that failed by tendon rupture (P=0.004). There was a significant decrease in bone mineral density with age (P=0.004), and the difference in age between the avulsed and ruptured specimens was close to statistical significance (P=0.058). For the avulsed specimens, there was a significant linear relationship between failure load and bone mineral density squared (P=0.002). Logistic regression indicated that the effect of age on failure mode is secondary to the primary effect of bone mineral density. CONCLUSIONS: The avulsions were primarily "premature" failures associated with low bone mineral density. Since bone mineral density decreases with age, older individuals are more likely to experience avulsions while younger individuals are more likely to experience tendon ruptures.

Mechanical properties of the human achilles tendon.

OBJECTIVE: To determine whether the human Achilles tendon has higher material properties than other tendons and to test for strain rate sensitivity of the tendon. DESIGN: Mechanical testing of excised tendons. BACKGROUND: While the human Achilles tendon appears to experience higher in vivo stresses than other tendons, it is not known how the Achilles tendon's material properties compare with the properties of other tendons. METHODS: Modulus, failure stress, and failure strain were measured for excised human Achilles tendons loaded at strain rates of 1% s(-1) and 10% s(-1). Paired t-tests were used to examine strain rate effects, and average properties from grouped data were used to compare the Achilles tendon's properties with properties reported in the literature for other tendons. RESULTS: Failure stress and failure strain were higher at the faster strain rate, but no significant difference in modulus was observed. At the 1% s(-1)rate, the mean modulus and failure stress were 816 MPa (SD, 218) and 71 MPa (SD, 17), respectively. The failure strain was 12.8% (SD, 1.7) for the bone-tendon complex and 7.5% (SD, 1.1) for the tendon substance. At the 10% s(-1) rate, the mean modulus and failure stress were 822 MPa (SD, 211) and 86 MPa (SD, 24), respectively. The mean failure strain was 16.1% (SD, 3.6) for the bone-tendon complex and 9.9% (SD, 1.9) for the tendon substance. These properties fall within the range of properties reported in the literature for other tendons. CONCLUSIONS: The material properties of the human Achilles tendon measured in this study are similar to the properties of other tendons reported in the literature despite higher stresses imposed on the Achilles tendon in vivo.

Interpretation of calcaneus dual-energy X-ray absorptiometry measurements in the assessment of osteopenia and fracture risk.

Dual-energy X-ray absorptiometry (DXA) of the calcaneus is useful in assessing bone mass and fracture risk at other skeletal sites. However, DXA yields an areal bone mineral density (BMD) that depends on both bone apparent density and bone size, potentially complicating interpretation of the DXA results. Information that is more complete may be obtained from DXA exams by using a volumetric density in addition to BMD in clinical applications. In this paper, we develop a simple methodology for determining a volumetric bone mineral apparent density (BMAD) of the calcaneus. For the whole calcaneus, BMAD = (BMC)/ADXA3/2, where BMC and ADXA are, respectively, the bone mineral content and projected area measured by DXA. We found that ADXA3/2 was proportional to the calcaneus volume with a proportionality constant of 1.82 +/- 0.02 (mean +/- SE). Consequently, consistent with theoretical predictions, BMAD was proportional to the true volumetric apparent density (rho) of the bone according to the relationship rho = 1.82 BMAD. Also consistent with theoretical predictions, we found that BMD varied in proportion to rho V1/3, where V is the bone volume. We propose that the volumetric apparent density, estimated at the calcaneus, provides additional information that may aid in the diagnosis of osteopenia. Areal BMD or BMD2 may allow estimation of the load required to fracture a bone. Fracture risk depends on the loading applied to a bone in relation to the bone's failure load. When DXA is used to assess osteopenia and fracture risk in patients, it may be useful to recognize the separate and combined effects of applied loading, bone apparent density, and bone size.

Mechanobiology of tendon adaptation to compressive loading through fibrocartilaginous metaplasia.

Tendons that wrap around bones often undergo fibrocartilaginous metaplasia. In this paper, we examine the biomechanical causes and consequences of this metaplasia. We propose an adaptation rule in which tissue permeability changes in response to local cyclic hydrostatic pressures associated with physical activity. The proposed rule predicts the development of a low-permeability region corresponding to the fibrocartilaginous region in a representative wrap-around tendon. A poroelastic finite element model is used to examine the time-dependent fluid pressures and compressive stresses and strains in the solid constituents of the tendon's extrafibrillar matrix. The low permeability in the adapted fibrocartilaginous region maintains fluid pressures, protecting the solid constituents of the tendon's extracellular matrix from high compressive stresses and strains that could disrupt the matrix organization. Adaptation through fibrocartilaginous metaplasia therefore allows wrap-around tendons to function effectively over a lifetime without sustaining excessive mechanical damage due to cyclic compressive loading.

Tendon and ligament adaptation to exercise, immobilization, and remobilization.

This study provides a theoretical and computational basis for understanding and predicting how tendons and ligaments adapt to exercise, immobilization, and remobilization. In a previous study, we introduced a model that described the growth and development of tendons and ligaments. In this study, we use the same model to predict changes in the cross-sectional area, modulus, and strength of tendons and ligaments due to increased or decreased loading. The model predictions are consistent with the results of experimental exercise and immobilization studies performed by other investigators. These results suggest that the same fundamental principles guide both development and adaptation. A basic understanding of these principles can contribute both to prevention of tendon and ligament injuries and to more effective rehabilitation when injury does occur.

A microstructural model for the tensile constitutive and failure behavior of soft skeletal connective tissues.

We propose a microstructural model for the uniaxial tensile constitutive and failure behavior of soft skeletal connective tissues. The model characterizes the tissues as two-phase composites consisting of collagen fibers embedded in ground substance. Nonlinear toe region behavior in the stress versus strain curve results from the straightening of crimped fibers and from fiber reorientation. Subsequent linear behavior results from fiber stretching affected by fiber volume fraction, collagen type, crosslink density, and fiber orientation. Finally, the tissue fails when fibers successively rupture at their ultimate tensile strain. We apply the model to tendon, meniscus, and articular cartilage. The model provides a consistent approach to modeling the tensile behavior of a wide range of soft skeletal connective tissues.

A model for loading-dependent growth, development, and adaptation of tendons and ligaments.

The geometric and material properties of tendons and ligaments change during growth and development. While some of the changes occur in the absence of mechanical loading, normal development requires the mechanical stimulus provided by normal physical activity. We have developed an analytical framework for quantitatively describing changes in uniaxial tendon and ligament properties throughout ontogeny. In our approach, cross-sectional area, modulus, and strength undergo baseline levels of development due to inherent time-dependent biological influences. The properties also change in response to mechanobiological influences by adapting to maintain a constant daily strain stimulus under changing load conditions. We have implemented a computer algorithm based on these concepts and obtained results consistent with experimental observations of normal tendon and ligament growth and development reported by other investigators. Additional results suggest that these concepts can also explain tendon and ligament adaptation to increased or decreased loading experienced during development.