 The zone of reserve cartilage exhibits no cellular prolif eration or active matrix production.  The zone of proliferation is adjacent to the zone of re serve cartilage in the direction of the diaphysis. In this zone of reserve cartilage zone of proliferation zone of hypertrophy zone of calcified cartilage zone of resorption bone osteoclast blood vessel osteoblasts
FIGURE 8.19 • Longitudinal section through the distal end of a metatarsal bone of a 2-month-old infant. The epiphyseal (secondary) ossification center is well formed. Bone formation is taking place at both the epiphyseal and the diaphyseal surface of the epiphyseal plate. The zonation is apparent on the diaphyseal side because the growth rate there is so much greater than the epiphyseal ossification center. Because both centers are active, the zone of reserve cartilage is relatively narrow. H&E 280. (Reprinted with permission from Kelly DE, Wood RL, Enders AC. Bailey’s Textbook of Microscopic Anatomy. Baltimore: Williams & Wilkins, 1978.) zone, the cartilage cells undergo division and organize into distinct columns. These cells are larger than those in the reserve zone and actively produce collagen (mainly types II and XI) and other cartilage matrix proteins.
 The zone of hypertrophy contains greatly enlarged (hypertrophic) cartilage cells. The cytoplasm of these cells is clear, a reflection of the glycogen that they normally accumulate (which is lost during tissue preparation). Chondrocytes in this zone remain metabolically active; they continue to secrete type I collagen while increasing their secretion of type X collagen. Hypertrophic chondrocytes also secrete VEGF, which initiates vascular invasion.
The cartilage matrix is compressed to form linear bands between the columns of hypertrophied cartilage cells.
 In the zone of calcified cartilage, the hypertrophied cells begin to degenerate and the cartilage matrix becomes calcified. The calcified cartilage then serves as an initial scaffold for deposition of new bone. Chondrocytes positioned in the more proximal part of this zone undergo apoptosis.
 The zone of resorption is the zone nearest the diaphysis. The calcified cartilage here is in direct contact with the connective tissue of the marrow cavity. In this zone, small blood vessels and accompanying connective tissue invade the region previously occupied by the dying chondrocytes.
They form a series of spearheads, leaving the calcified cartilage as longitudinal spicules. In a cross section, the calcified cartilage appears as a honeycomb because of the absence of the cartilage cells. The invading blood vessels are the source of osteoprogenitor cells, which will differentiate into bone-producing cells.
Bone deposition occurs on the cartilage spicules in the same manner as described for the formation of the initial ossification center.
As bone is laid down on the calcified spicules, the cartilage is resorbed, ultimately leaving a primary spongy bone. This spongy bone undergoes reorganization through osteoclastic activity and addition of new bone tissue, thus accommodating the continued growth and physical stresses placed on the bone.