Dynamic histomorphometric evaluation of human fetal bone formation

We have evaluated dynamic and static parameters of bone formation in femoral metaphyses collected from two human fetuses at 19 weeks of gestation. Tetracycline was administered to the mother at set intervals (2-5-2 day schedule) before interruption of pregnancy. Labels were distinct and sharply linear, suggesting a well organized calcification front at this early stage of mineralization. Mineral apposition rate (MAR) was fastest (4.1 ± 0.3 μm/d) in the periosteal (Ps) envelope, and about half that value in the endosteal envelopes (endocortical: 2.5 ± 0.1, cancellous 2.1 ± 0.1 μm/d). Because cellular activities may vary throughout the metaphyseal area, sections were arbitrarily separated in 0.75 mm layers starting from the growth plate. Three measured parameters decreased rapidly with increasing distance from the physis: Ps MAR: 4.9 to 2.3 μm/d, trabecular osteoid thickness: 5.9 to 1.2 μm, and cartilage volume (CgV/TV): 5.4% to 1.2%. Others did not vary significantly along the metaphysis. Comparison of several static parameters with those measured in five autopsy specimens from full-term infants showed that bone and cartilage volume, and trabecular thickness increased while osteoid thickness and parameters of resorption decreased in the second half of the gestation period. The study indicates that fetal bone matrix mineralization is already highly organized at mid-gestation, and validates the use of histomorphometry to assess bone maturation during early skeletal development.