The effect of dynamic loading on the growth of epiphyseal cartilage in the rat

The Hueter-Volkmann law of epiphyseal pressures describes an inverse relationship between static compressive forces parallel to the axis of epiphyseal growth and the rate of growth of that cartilage. Studies of histological sections of the epiphyseal plate of the fourth metatarsals of (a) control, (b) bipedal and (c) bipedal rats with amputation of the fifth metatarsal show that dynamic compressive forces can stimulate epiphyseal cartilage growth. Within certain parameters, both the relief and increase of dynamic compression accelerate epiphyseal growth. It is the amount and kind of loading that are important factors to accelerate epiphyseal growth.     

Femoral neck anteversion: values, development, measurement, common problems

The femoral neck anteversion angle is an important factor for hip stability and normal walking. It is multifactoral result of evolution, heredity, fetal development, intrauterine position, and mechanical forces. Abnormal FNA sometimes can be associated with many clinical problems ranging from harmless intoeing gait in the early childhood, to disabling osteoarthritis of the hip and the knee in the adults. In most cases is associated with minor functional problems in children during growth, but cause a concern in parents for children future. The child must be examined carefully and an accurate diagnosis must be established. The most important part of care is observation of the children. If abnormal femoral neck anteversion produces severe functional disability, derotational osteotomy should be done, but delayed until late childhood.     

Stress changes in the femoral head due to porous ingrowth surface replacement arthroplasty

Finite element stress analyses were conducted of the canine femoral head before and after implantation of various surface replacement-type components. The femoral head was replaced by four implant geometries; (a) shell, (b) shell with peg, (c) shell with rod, and (d) a new epiphyseal replacement design. All implants were modelled to simulate bony ingrowth along the underside of the shell and along the surfaces of the peg and rod. The results indicated that in the normal femur the forces are transferred from the articular surface through the femoral head cancellous bone to the inferior cortical shell of the femoral neck. After shell-type surface replacement, forces were transferred more distally at the rim of the shell and at the end of the peg or rod, thereby reducing the stresses in the proximal head cancellous bone. Computer simulation of bone remodelling due to proximal bone stress reduction was shown to accentuate the abnormality of the stress fields. Surface replacement with a lower modulus material created a less abnormal redistribution of bone stresses. The new epiphyseal replacement design resulted in stress distributions similar to those in the normal femoral head and minimal shear stresses at the implant/bone interface. These findings suggest that the epiphyseal replacement concept may provide better initial mechanical integrity and create a more benign milieu for adaptive bone remodelling than conventional, shell-type surface replacement components.     

Anteversion versus torsion of the femoral neck.

The usual term 'torsion angle of the femur' denotes the 'anteversion' of the neck of the femur as a whole, caused by the twist in the shaft of the femur rather than the twist in the neck. This has been differentiated from the twist in the neck of the femur around its own axis, termed 'torsion neck' and the values of both have been measured. To differentiate these two different phenomena, the term 'anteversion' is used to denote the usual angel described, while 'torsion neck' is sued to denote the twist in the neck around its own axis measured in this work. 1,000 femora from 21 cites in different parts of the country have been measured and the average anteversion angle calculated. The Indian average works out to be 12 degrees with a significantly (double) high value for females. The incidence of negative angle is 7% in the normal femora. All fractured femora invariably show a negative angle. The above information should be of great significance on orthopaedic surgery of the neck of the femur in these bones. The 'torsion neck' has been measured by tracing and its average reported as 30 degrees.     

The safe-zones for combined cup and neck anteversions that fulfill the essential range of motion and their optimum combination in total hip replacements

Reduction of the range of motion (ROM) until prosthetic impingement of a total hip replacement may lead to frequent impingement, subluxation and dislocation especially for patients with good hip movement. The ROM until prosthetic impingement can be calculated using the technical ROM (theta) and the cup and neck positions by a previously created mathematical formula. A larger (theta) with proper cup and neck positions results in a larger ROM. However there was only one paper written in English, which revealed the optimum theoretical combination of cup and neck anteversions. ROM of more than 110 degrees flexion, 30 degrees internal-rotation at 90 degrees flexion, 30 degrees extension and 40 degrees external-rotation were defined as the criteria for essential ROM for ADL. The safe-zones for combined cup anteversion (betaanat) and neck anteversion (b) were defined as the areas that fulfill all the criteria of ROM without prosthetic impingement. The safe-zones were created for 35 degrees , 45 degrees and 55 degrees cup abductions (alpha) and for 120 degrees and 135 degrees (theta). The safe-zones for combined (betaanat) and (b) were much larger for a 135 degrees (theta) than a 120 degrees (theta). Their safe-zones showed that (b) should be reduced if (betaanat) is increased and choosing a lower (alpha) requires that the sum of (betaanat) and (b) should be higher and vice versa. A (theta) of more than 135 degrees is recommended as it further increases the size of the safe-zone and provides a larger ROM, and the optimum values of combined cup and neck anteversions can be estimated by the formula: (alpha) + (betaanat) + 0.77(b) = 84.3.     

Development of epiphyseal structure and function in Didelphis virginiana (Marsupiala,Didelphidae)

This study addressed the question of how the epiphyses of growing mammals change their external shape and internal architecture during postnatal development. Ontogenetic transformations in the external form and internal structure of the fore‐ and hindlimb epiphyses were examined in a mixed cross‐sectional sample of Didelphis virginiana using two methods: morphometric analysis of linear epiphyseal dimensions and histological staining of serially sectioned epiphyses. Metric data indicate that Virginia opossums are born with relatively short hindlimbs and long forelimbs, but by the time they are weaned their hindlimbs are longer than their forelimbs. Functional integration of the locomotor system in D. virginiana involves a decoupling of fore‐ and hindlimb growth rates so that between birth and weaning, femoral length, diaphyseal cross‐sectional area, and articular surface area increase at a significantly faster rate than the corresponding humeral dimensions. Histological results demonstrate that these differences in growth rate are reflected in morphology of the humeral and femoral growth plate and epiphyseal cartilages. The humeral cartilages exhibit a level of cellular organization characteristic of more mature limb elements at earlier developmental stages compared to the femoral cartilages, which assume this anisotropic structure relatively later in postnatal development. Results presented here also reveal that the formation of articular cartilage and the initiation of epiphyseal ossification in D. virginiana are both correlated with the development of independent positional behaviors prior to weaning. These histological data, therefore, suggest that mechanical loading associated with the postnatal onset of locomotor and postural development may provide an important stimulus for the progression of ossification and the formation of articular cartilage in the epiphyses of growing mammals. J. Morphol. 239:283–296, 1999. © 1999 Wiley‐Liss, Inc.     

Effects of chondroitin sulphates on mineralization in vitro

1. Soluble sodium chondroitin sulphate, from bovine ribs or puppy epiphyseal plate, at a concentration 80mm in terms of glucuronate, decreased the amounts of calcium and phosphate precipitated from a solution 6.9mm in phosphate and 6.9 or 13.8mm in calcium, buffered in the pH range 6.6-8.2 with 20-25mm-collidine and 5-20mn-hydrochloric acid when incubated for 2hr. at 30 degrees , and for 0.25-24hr. when buffered at pH7.0. 2. An insoluble fraction of puppy epiphyseal plate, containing chondroitin sulphate and collagen, was found to have the same effect at lower concentrations of chondroitin sulphate and a higher calcium/chondroitin sulphate glucuronate ratio, but the formation of calcium phosphate from calcium bound to this material appeared to proceed more rapidly than from calcium in solution, when both were present in the same system. 3. The implications of these results are discussed in relation to the calcium/chondroitin sulphate glucuronate ratios found in different parts of non-calcifying and calcifying cartilage in vivo and to the calcium and phosphate gradients between blood and calcified tissue.     

Relation between increase in length of hip axis in older women between 1950s and 1990s and increase in age specific rates of hip fracture.

OBJECTIVE--To determine whether length of hip axis in elderly women has increased over the past 40 years and, if so, whether the increase may have contributed to the increase in the age adjusted rate of hip fractures during those years. DESIGN--Retrospective assessment of anteroposterior x ray films of the pelvis. SETTING--Radiology department of a rheumatology hospital, New Zealand. PATIENTS--Two cohorts of women aged > 60 (mean 70) who were x rayed on the same apparatus in either the 1950s or the 1990s. MAIN OUTCOME--Length of hip axis (distance from the medial aspect of the pelvis to the lateral aspect of the femur along the axis of the femoral neck), length of femoral neck (length of hip axis excluding the femoral head and more medial structures), and width of femoral neck (see figure). RESULTS--Both the mean length of the hip axis and the mean length of the femoral neck were significantly greater in the women whose x ray films were taken in the 1990s than in those in the 1950s (124.0 mm (SE 1) v 130.5 (1), P = 0.0002; 79.4 (1) v 84.9 (1), P < 0.0001, respectively). The width of the femoral neck did not change, and the lengths expressed as ratios to width were greater in the more recent x ray films, indicating that these findings are not due to an unrecognised change in radiographic technique. CONCLUSIONS--An increase in the length of the hip axis in elderly women in New Zealand during the past 40 years has occurred which is large enough to account for the increase in the age adjusted rate of hip fractures during those years.     

Phagocytosis of dying chondrocytes by osteoclasts in the mouse growth plate as demonstrated by annexin-V labelling

Endochondral ossification in the epiphyseal growth plate of long bones is associated with programmed cell death (PCD) of a major portion of the chondrocytes. Here we tested the hypothesis that at the ossification front of the epiphyseal growth plate osteoclasts preferentially phagocytose chondrocytes that are undergoing PCD. We injected biotin-labelled annexin-V (anx-V-biotin, an early marker of PCD) intravenously in young adult mice. After 30 min of labelling, long bones were recovered and the tissue distribution examined of anx-V-biotin-labelled cells in the growth plate using ABC-peroxidase histochemistry. Positive staining for anx-V-biotin was detected in hypertrophic chondrocytes still present in closed lacunae at some distance from the ossification front. At the ossification front, chondrocyte lacunae were opened and close contacts were seen between tartrate-resistant acid phosphatase-positive osteoclasts and hypertrophic cartilage cells. Osteoclasts were significantly more frequently in contact with anx-V-biotin-labelled chondrocytes than with unlabelled chondrocytes. Osteoclasts also contained labelled and unlabelled phagocytic fragments within their cytoplasm. We conclude that in the growth plate osteoclasts preferentially phagocytose hypertrophic chondrocytes that are dying, suggesting these dying cells may signal osteoclasts for their removal.     

Hominid femoral neck length

Human femoral neck length has a positive allometric or isometric relationship with total femoral length as shown by the reduced major axis slope based on logarithmic regression. The relatively long femoral neck lengths of Australopithecus cannot be explained solely as a consequence of small body size (contra Wolpoff, '78).     

A femoral neck fracture model in rabbits

A technique was developed to create a reproducible femoral neck fracture in vitro using 5-month-old JW/CSK series male rabbits. Force attenuation of a newly developed damping material was also evaluated using this model. Ten pairs of the femora with smaller deviations in length and weight were harvested and cleaned of soft tissue. Either a right or left of each pair of the specimens was randomly selected and put into either the control or the experimental group, both of which contained equal numbers of the right and left femora. The specimens were attached to an L-shaped plate and embedded in a resin from the proximal diaphysis to the distal end so as to maintain a consistent position of the femora. They were mounted and fixed on a pedestal slanted in the coronal plane at 20 degrees. The impact load testing was conducted using an impact mallet dropped from a height of 3 cm. The impact load was applied onto the femoral head. To the specimens in the experimental group, attenuated impact forces were loaded through the damping material, but those in the control group were subjected to forces directly transmitted without the material. All the impact testing was performed in a temperature and humidity controlled chamber. All of the femoral specimens exposed to the direct impact forces (controlled group) sustained fracture at the neck. The fracture line passed from the base of the femoral head laterally and to the calcar area just proximal to the minor trochanter medially. The location of each fracture line was almost identical among the specimens. None of the specimens that were exposed to the impact force through the damping material (experimental group) sustained fracture macroscopically and roentgenographically.     

Phosphomonoesterases in growth cartilages of the rat

Summary Epiphyseal plate cartilage, epiphyseal cartilage, synchondroseal cartilage and mandibular condylar cartilage were studied morphologically and histochemically in 14 days old rats. Ordinary decalcified paraffin sections were stained with hematoxylin & eosin, van Giesons connective tissue stain, or toluidine blue, and used for morphological studies of the different cartilaginous structures. Undecalcified cryostat sections were used for demonstration of acid and alkaline phosphatase. The enzyme activity was tested for at regular intervals during incubation from 15 sec to 120 min.The morphologic study revealed that a marked similarity of construction exists between epiphyseal plate cartilage and synchrondroseal cartilage. The construction of epiphyseal and condylar cartilage differ from that of the other two structures and also differ mutually.With small variations the reaction for both alkaline and acid phosphatase was found to be identical in the zones of erosion, hypertrophy and maturation of the four structures. Intercellularly, acid phosphatase is present in all zones in the synchondroseal and the epiphyseal plate cartilage, while in the epiphyseal and condylar cartilages it is only present in the zones of erosion, hypertrophy and maturation.The identical reaction for acid phosphatase in the epiphyseal and the condylar cartilage is thought, in all likelihood, to be accidental. When kinetic conditions are taken into account, epiphyseal cartilage seems to react like epiphyseal plate and synchondroseal cartilage, while the condylar cartilage takes up an exceptional position among growth cartilages.     

Femoral anteversion influences vastus medialis and gluteus medius EMG amplitude: composite hip abductor EMG amplitude ratios during isometric combined hip abduction-external rotation.

This prospective study evaluated differences in vastus medialis (VM) and gluteus medius (GM) EMG amplitude:composite hip abductor (gluteus maximus, gluteus medius, tensor fascia lata) EMG amplitude ratios among subjects with low or high relative femoral anteversion. Data were collected during the performance of a non-weight bearing, non-sagittal plane maximal volitional effort isometric combined hip abduction-external rotation maneuver. Eighteen nonimpaired athletically active females participated in this surface EMG study. Medial hip rotation (relative femoral anteversion estimate) was measured with a handheld goniometer. Subjects were grouped by medial hip rotation displacement (group 1 < or = 42 degrees =36.1+/-7 degrees and group 2 > 42 degrees =52.7+/-7 degrees ) for statistical analysis (Mann Whitney U-tests, p < 0.05). Group 2 had decreased VM (42+/-23% vs. 69+/-30%, U=19, p=0.034) and GM (62+/-25% vs. 96+/-39%, U=19, p=0.034) normalized mean peak EMG amplitude:composite mean peak hip abductor EMG amplitude ratios compared to group 1. Decreased normalized VM (-27%) and GM (-34%) EMG amplitudes among subjects with increased relative femoral anteversion suggest reduced dynamic frontal and transverse plane femoral control from these muscles, possibly contributing to the increased incidence of non-contact knee injury observed among athletic females.     

Epiphyseal-based designs for tibial plateau components--II. Stress analysis in the sagittal plane

A two-dimensional, finite element study was undertaken to establish the stresses in the proximal tibia before and after total knee arthroplasty. Equivalent-thickness models in a sagittal plane were created for the natural, proximal tibia and for the proximal tibia with two different types of tibial plateau components. All components simulated bony ingrowth fixation, i.e. no cement layer existed between component and bone. In addition, the interface between component and bone was assumed to be intimately connected, representing complete bony ingrowth and a rigid state of fixation. Two load cases were considered: a joint reaction force acting in conjunction with a patellar ligament force, simulating the knee at 40 degrees of flexion; and a joint reaction force directed along the long axis of the tibia. For the natural tibia model, the pattern of principal stresses for loadcase 1 more closely corresponds to the epiphyseal plate geometry and trabecular morphology than do the principal stress patterns for loadcase 2. Judging from the distribution of principal stresses, loadcase 1 represents a more severe test of implant design than does loadcase 2. The model of the component with a peg predicted that the trabecular bone near the tip of the peg will experience higher than normal stresses, while the bone stresses near the posterior aspect adjacent to the metal tray will be reduced. A component without pegs that incorporates a posterior chamfer and an anterior lip lead to stress distributions closer to those existing in the natural tibia. The interface geometry for this design is based upon the contour of the epiphyseal plate.     

Mechanobiological prediction of proximal femoral deformities in children with cerebral palsy

Children with cerebral palsy (CP) walk with altered gait and frequently exhibit proximal femoral deformities, such as anteversion and coxa valga. The objective of this research was to investigate the effect of specific gait patterns on the femoral morphology in CP.

In this study, the mechanobiological principles were implemented on a 3D finite element (FE) model of the proximal femur in order to predict changes in morphology over time in healthy and CP children. This model relies on the assumption that cyclic octahedral shear stress promotes growth and cyclic hydrostatic compressive stress inhibits growth. Growth was simulated over 16 iterations, representing approximately 5 months of growth.

The FE model predicts an increase in the femoral anteversion and coxa valga for CP loading conditions when compared with healthy ones. Understanding the role of loading in skeletal morphogenesis may help prevent bone deformities and improve function in children with gait abnormalities.     

The role of autocrine growth factors in radiation damage to the epiphyseal growth plate

Radiation therapy plays an important role as part of the multimodality treatment for a number of childhood malignancies. Dose-limiting complications of radiotherapy include skeletal abnormalities and disturbances in skeletal development within the irradiated field. The current study was undertaken to investigate the molecular mechanisms involved in radiation-induced arrest of bone growth. Our hypotheses were: (1) Expression of autocrine growth factors that regulate chondrocyte proliferation is inhibited by radiation in a specific pattern; (2) the disparity in radiosensitivity of growth plate chondrocytes and epiphyseal chondrocytes is due to differential modulation of autocrine growth factor expression by radiation. Given the important role these cells play in skeletal growth and development, we examined the comparative effects of radiation on expression of specific mitogenic growth factors in growth plate chondrocytes. The effect of radiation on the expression of autocrine/paracrine growth factors was examined in an established avian model of epiphyseal growth plate maturation. Exposure of growth plate chondrocytes to radiation resulted in a specific pattern of biochemical and morphological alterations that were dependent on dose and were progressive over time. While radiation did not affect the mRNA expression of some of the autocrine and paracrine factors important in endochondral ossification (such as FGF2 and TGFB isoforms), it did lead to a decrease in the mRNA expression of PTHrP, a critically important mitogen in growth plate chondrocytes, and a dose-dependent decrease in the PTH/PTHrP receptor mRNA. Interestingly, PTHrP mRNA levels were not affected in irradiated epiphyseal chondrocytes, the main source of PTHrP. Given evidence indicating a role for intracellular calcium levels in regulating PTHrP expression, basal calcium levels in irradiated growth plate chondrocytes and epiphyseal chondrocytes were examined 24 h after treatment. While cytosolic calcium levels were significantly higher in irradiated growth plate chondrocytes, they were not significantly affected in irradiated epiphyseal chondrocytes. The importance of calcium in mediating radiation damage to growth plate chondrocytes was further demonstrated by the finding that the addition of 4.0 mM EGTA (a calcium chelator) to the cell cultures before irradiation prevented the decrease in PTHrP mRNA levels. Since PTHrP up-regulates BCL2 levels and prevents growth plate chondrocyte maturation and apoptosis, BCL2 mRNA levels were examined in irradiated growth plate chondrocytes, and a dose-dependent decrease was found. An increase in apoptosis was further confirmed by a fivefold increase in caspase 3 levels in irradiated growth plate chondrocytes. The results of the current study suggest that radiation may interfere with proliferation of growth plate chondrocytes in part by causing an increase in cytosolic calcium levels which in turn leads to a decrease in PTHrP mRNA. Growth plate chondrocyte PTHrP receptor mRNA expression is also inhibited by radiation, further decreasing PTHrP signaling. Despite subtle differences between the chick and mammalian growth plates, further studies should provide an enhanced understanding of the mechanism(s) of radiation injury to the growth plate, as well as possibilities for new therapeutic strategies to protect the growing skeleton from the detrimental effects of radiotherapy.     

The epiphyseal cartilage and growth of long bones in Rana catesbeiana.

The structure of the epiphyseal cartilage of the bullfrog Rana catesbeiana and its role in the growth of long bones were examined. The epiphyseal cartilage was inserted into the end of a tubular bone shaft, defining three regions: articular cartilage, lateral articular cartilage and growth cartilage. Joining the lateral cartilage to the bone was a fibrous layer of periosteum, rich in blood vessels. Osteoblasts with alkaline phosphatase activity were found on the surface of the periosteal bone, which presented a fibrous non-mineralised tip. The growth cartilage was inside the bone. The proliferative chondrocytes presented perpendicular separation of daughter cells and there was no columnar arrangement of the cells. Furthermore, chondrocyte hypertrophy was not associated with either calcification or endochondral ossification, in apparent contrast to the avian and mammalian models. Finally, there was no reinforcement system capable of directing cell volume increase into longitudinal growth. Since bone extension depends on the intramembranous ossification of the periosteum, the growth cartilage is inside and not at the end of the bone and the cells in the growth cartilage show no columnar arrangement and separate in a direction perpendicular to the long bone axis, we conclude that the growth cartilage mainly contributes to the radial expansion of the bone.     

Electrical stimulation of the growth plate: a potential approach to an epiphysiodesis

Epiphysiodesis is an operative procedure that induces bony bridges to form across a growth plate of a bone to stop longitudinal growth. This is a very common orthopedic procedure to correct disproportional long-bone growth discrepancies; however, present techniques require an operation and anesthesia. Our study was designed to develop a minimally invasive method of epiphysiodesis by using electrical stimulation with DC current. In a rabbit model, a thin titanium electrode was inserted into a single location of the distal femoral growth plate in three groups: one without current (control), one group with a constant 10 microA (low current, LC), and one group with a 50 microA (high current, HC). The current was delivered for 2 weeks. The nontreated femur served as a control for each animal. Femur lengths were measured and comparisons were made between operated (left) and nonoperated (right) femurs. Digitized histomorphometric and volumetric analyses were performed on each growth plate, and detailed assessments were made of any morphological changes. Using length measurements, the difference in femur length was significantly larger in the HC group and not in the LC or control groups, showing bone growth inhibition at the higher current. In the HC group, bony bridges and disorganized growth plates were observed. This study shows that delivery of an electrical current of 50 microA for as little as 2 weeks can markedly affect bone growth as evidenced by changes in epiphyseal plate volume and architectural organization, and the study supports the use of this minimally invasive approach as a potential method of achieving an epiphysiodesis.     

Femoral neck fracture is accompanied by local changes in the content of transforming growth factor-beta1, interleukin-1beta and collagenase activity

The aim of the study was to evaluate the relationship between the time from femoral neck fracture and the content of transforming growth factor-beta1 (TGF-beta1), interleukin-1beta (IL-1beta) and collagenase activity in bone samples of the femoral neck. The material consisted of 42 cancellous bone samples from the femoral neck collected from patients after the femoral neck fracture during hip replacement procedure. The content of TGF-beta1, IL-1beta in bone samples was measured with the use of enzyme-linked immunoassay (ELISA) and collagenase activity was measured with spectrofluorimetry. The mean content of TGF-beta1/total protein was 2.29 pg/microg (range from 0.9 to 4.0). The mean content of IL-1beta was 4.93 fg/microg (range from 1.4 to 12.5). The mean activity of collagenase was 49.08 nU/microg (range from 5.6 to 113.7). The content of TGF-beta1 and IL-1beta decreased after the injury. In case of TGF-beta1 the difference was statistically significant (p<0.05). The activity of collagenase was statistically significantly increasing in relation to time from the fracture (p<0.05). We found no correlation between the content of TGF- beta1, IL-1beta and the activity of collagenase and the age and the sex of the patients. Also, no significant discrepancies were found between the examined cytokines in relation to the bone loss of the femoral neck according to Singh's scale. These results confirm mutual changes of activity between examined cytokines in the area of fractured bone.     

Use of microarray analysis to study gene expression in the avian epiphyseal growth plate

Longitudinal bone growth depends upon the execution of an intricate series of cellular activities by epiphyseal growth plate chondrocytes. In order to better understand these coordinated events, microarray analysis was used to compare gene expression in chondrocytes isolated from the proliferative and hypertrophic zones of the avian growth plate. RT-PCR was used to confirm the identity of a select number of genes. The expression of 745 genes was found to differ 3-fold or greater at the 0.05 level of probability. Transferrin was the most highly up-regulated (321-fold) gene associated with chondrocyte hypertrophy. Immunohistochemistry localized this peptide adjacent to the penetrating blood vessels in the growth plate of 3-week-old chicks. Fibulin, OC-116, DMP-1 and PHEX were among the expanded number of genes associated with extracellular matrix metabolism. The presence of NELL2, ATOH8 and PLEXIN suggests a neuronal involvement in growth plate physiology. In addition, the expression of a large number of genes associated with angiogenesis and cellular stress was up-regulated. These processes are important to the physiology and survival of chondrocytes in the unique and stressful environment of the epiphyseal growth plate.