Our current understanding of the pattern of closure of the distal tibial physis is based on radiographic, magnetic resonance imaging, and qualitative histological studies. Kleiger and Mankin in 1964 reviewed the radiographs of 22 ankles in the process of physeal closure and found that it proceeded in an asymmetrical pattern. The physis appears to close in the middle first, then on the medial side, and then the lateral portion. This assessment has been reaffirmed by the work of Kump [2
] and Ogden [1
]. Chung and Jarmillo [4
] analyzed the magnetic resonance imaging sequences of 14 patients who were felt to be undergoing normal physiological epiphysiodesis. These authors observed, by means of MRI, that closure appeared to start at the undulation in the anteromedial physis and proceed laterally. Love et al. [5
] performed a routine (non-optimized) histological examination of 44 distal tibiofibular composites from cadaver or amputation specimens from age birth to 15 years. In this study, physiological epiphysiodesis occurred between the ages of 12 and 14 years in girls and between the ages of 15 and 18 years in boys. Closure was seen, characteristically, to occur in a medial to lateral pattern over a period of 1.5 years.
The subject of the current study was almost 13 years of age at the time of amputation. Her chronological age would suggest that she was in the period of physiological epiphysiodesis, and our findings support this. Our patient’s growth plate was closing in the central portion, a finding which corresponds to previous results in the literature. We anticipated that the medial portion would close before the lateral side, in concordance with previous reports.
This study provided a unique opportunity to examine a human distal tibial physis with optimal chemical fixation in the presence of RHT, thus allowing analysis using stereological methodologies. We realize that in our phenomenological study of this patient’s growth plate, there is a limited ability to extrapolate to other human growth plates. Although not directly involved in disease, our patient and this physis experienced abnormal loading and was exposed to chemotherapy. Doxorubicin and cisplatin result in decreased growth rate and final height [13
]. Therefore, the growth rate and timing of closure may have been affected by the previous treatment, although any effect on the pattern of physeal closure is unknown.
The organized cellular columns evident in an actively growing physis are disrupted in this growth plate. Furthermore, the cells in this specimen are organized into tightly packed clusters with large intervening areas of acellularity. Interestingly, the histological findings are consistent with those found in a rat physis after cessation of growth [14
]. With respect to comparative biology of physes from different mammalian species, a case could be made that the “classical” proximal tibial growth plates from rabbits and rats (even mice) are extremes of growth plate structure and physiology. These growth plates have a physiological growth velocity of between 300 and 600 μm/day that depends on age, perhaps a 10–20× faster growth velocity than human growth plates. In addition, when the histological arrangement of growth plates with a slow growth velocity is observed, the trend is for chondrocytes to be less arranged in columns and more arranged in clonal clusters [15
In this growth plate, the average hypertrophic cell volume was 5,900 μm3
, with no significant difference between the different zones of the physis. In contrast, hypertrophic cell volume in adolescent rats is about 15,000 μm3
. In a histological analysis of a human growth plate from a 10-year-old girl [13
], Hall and Macnicol [16
] found hypertrophic cell volumes from 621 to 1,572 μm3
. It is hard to draw comparisons between our study and theirs. In the previous paper, their patient was [2
] years younger, the cells were from the proximal tibial and distal femoral physes, and the patient had hemihypertrophy of the affected limb. Most importantly, their sample was prepared and analyzed using different techniques. Our sample was prepared with optimum chemical fixation, and a large population of hypertrophic chondrocytes from throughout the growth plate was sampled. If we measure physeal chondrocyte just proximal to the most distal 100-μm hypertrophic chondrocytes, these cells have a volume similar to that previously reported. Regardless of mammalian species, enlargement of hypertrophic chondrocyte through a process of “matrix directed cellular swelling,” is now recognized as the “chief engine of growth and the chief regulatory cell” [17
]. As previously stated, our patient had undergone treatment with chemotherapeutic agents that slow skeletal growth, and the hypertrophic cell volume results must be interpreted in that context. The patient had not been exposed to doxorubicin and adriamycin for 13 months and the lasting effects on the hypertrophic cell volume is unknown. Despite this limitation, it is interesting to see that cessation of growth in this sample does not appear to be accompanied by decreases in cell volume in this subject; obviously, other mechanisms are needed to lead to growth cessation.
This study provided a unique opportunity to apply optimum fixation and current stereological techniques to a human distal tibial physis during the earliest phases of physiological epiphysiodesis. Using optimum fixation techniques, the human hypertrophic cell volume at this stage was found to be 5,900 μm 3. The current specimen provides quantitative support using modern stereological techniques that the distal tibial physis begins closure in the central portion.