Features of the appearance of primary ossification centers in humans

Abstract

Digital data of computer tomograms of primary centers of ossification in human fetuses can serve as age-normative intervals relevant for gynecologists, obstetricians, pediatricians, and diagnosticians during screening ultrasound examinations.

Aim - to clarify the timing of the emergence of primary centers of ossification and the dynamics of further development of human bone deposits for estimating fetal age and for ultrasound diagnosis of congenital malformations.

Materials and methods. The study was carried out on 32 series of consecutive sagittal, frontal, and horizontal sections of human embryos and pre-fetuses aged from 4 to 12 weeks of intrauterine development (IUD) 4.0-80.0 mm parietal-coccygeal length (TCL) and 54 preparations of human fetuses 4-7 months (81.0-270.0 mm TCL) using a microscopic method, computer tomography and creation of 3D-reconstruction models of pre-fetuses and human fetuses of various ages. Three-dimensional computer reconstruction was applied to study, the morphometry and densitometry of serial CT sections. The DICOM PACS standard series of images were processed in specialized computer programs RadiAnt Dicom Viewer (Medixant), and ImageJ (National Institutes of Health). Such programs automatically outline the contours of the bone model according to the gradients of the Hounsfield scale, which allows you to visualize and carry out morphometry of the entire bone model and the ossification centers.

Results. At the end of the 6th week of embryonic development, there is an accumulation of mesenchyme in the area of the future cartilaginous models of the skeleton, this is the pre-cartilaginous stage of osteogenesis, which is well expressed in the area of the future cartilaginous model of the spine. At the beginning of the 8th week of IUD, the cartilaginous structure of the ribs, limb bones, pelvis, and vertebral bodies was revealed. In the bodies of the vertebrae, there is a tendency towards the processes of ossification, which is expressed in the uneven staining of the intercellular substance, which acquires a dark color in places. In this age period, three points of bone tissue attachment appear, located in the area of the upper and lower jaws, and the clavicle. At the end of the 8th - at the beginning of the 9th week of IUD, the intensity of bone tissue deposits in the clavicle and jaws, especially the upper jaw, increases significantly. In 9-week-old human fetuses, the parts of the rib are clearly defined on a series of histological sections: head, neck, and body. In the area where the ribs join the vertebrae, there is a border between the bone part of the rib and its head. In 11-week-old human fetuses, numerous and diverse foci of ossification are determined in many bones of the skeleton. Taking into account the fact that the contraction of the muscles of the fetus begins from the 3rd month of intrauterine life, from this moment the contracting muscles affect the design of the details of the skeleton structure, namely, the processes of the arches and bodies of the vertebrae. In models of tubular bones of the lower and upper limbs, intensive concentric bone deposition is present, while in other ossification centers, bone deposition is mainly observed in the form of plates of various shapes and sizes, connected by thinner bone cords. In fetuses of 6-7 months, ossification of the pelvic bones is clearly expressed. The process of ossification almost completely covers the posterior parts of the ilium, except for its lower parts and cartilaginous areas adjacent to the iliac crest. Intensive deposition of bone mass is found in the area of the buttock.

Conclusions. For the first time, the primary centers of ossification in human embryos appear at the age of 1.5 months and are located in the clavicle and upper and lower jaws. In the future, the ossification process dynamically increases and becomes more complicated, proceeding specifically with certain features for each future bone. The deposition of bone masses of different shapes and sizes is expressed unevenly in individual parts of the skeleton.

The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies.

No conflict of interests was declared by the authors.