Injury, Int. J. Care Injured (2007) 38, 1115—1130 www.elsevier.com/locate/injury REVIEW The periosteum Part 1: Anatomy, histology and molecular biology Goran Augustin *, Anko Antabak, Slavko Davila Clinical Hospital Center Zagreb, Kisˇpatic´eva 12, 10000 Zagreb, Croatia Accepted 21 May 2007 KEYWORDS Summary The periosteum is a thin layer of connective tissue that covers the outer Periosteum; surface of a bone in all places except at joints (which are protected by articular Fibrous layer; cartilage). As opposed to bone itself, it has nociceptive nerve endings, making it very Cambium layer; sensitive to manipulation. It also provides nourishment in the form of blood supply to Sharpey’s fibres; the bone. The periosteum is connected to the bone by strong collagenous fibres called Periosteal circulation; Sharpey’s fibres, which extend to the outer circumferential and interstitial lamellae Bone formation; of bone. The periosteum consists of an outer ‘‘fibrous layer’’ and inner ‘‘cambium Bone resorption; layer’’. The fibrous layer contains fibroblasts while the cambium layer contains Perichondrial progenitor cells which develop into osteoblasts that are responsible for increasing ossification groove bone width. After a bone fracture the progenitor cells develop into osteoblasts and chondroblasts which are essential to the healing process. This review discusses the anatomy, histology and molecular biology of the periosteum in detail. # 2007 Elsevier Ltd. All rights reserved. Contents Historical aspects . 1116 Anatomical considerations . 1116 Microscopic features . 1116 Periosteal circulation . 1120 Intrinsic periosteal system . 1121 Periosteocortical (cortical capillary) anastomoses . 1122 Musculoperiosteal system . 1122 Nutritive periosteal system (fascioperiosteal system) . 1122 Periosteal bone formation during growth . 1123 Periosteal bone formation in adulthood . 1124 Periosteal bone resorption. 1125 The perichondrial ossification groove . 1126 * Corresponding author. Tel.: +385 915252372. E-mail addresses: [email protected] (G. Augustin), [email protected] (A. Antabak), [email protected] (S. Davila). 0020–1383/$ — see front matter # 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.injury.2007.05.017 1116 G. Augustin et al. Extrinsic mechanical effects of the periosteum on the growth plate . 1126 Conflict of interest statement . 1127 References. 1127 Historical aspects chanical features: bone fractures without the dis- ruption of the periosteum (subperiosteal fractures) Since the time of Duhamel and John Hunter it has or intact periosteum on the concave side of the 59 been the belief of anatomists and surgeons that the fracture (greenstick fracture). With growth, the periosteum is osteogenic. In 1757 Duhamel and periosteum becomes thinner and loses elasticity and 91 Monceau reflected the periosteum from the bone firmness. It is especially compliant on tensile and fitted around it a silver ring, over which the forces and tearing which results in the disruption periosteum was sewed. After a period of several of the periosteum in the level of bone fracture in months the ring was completely covered with bone adults. The periosteum is highly vascularised and and from this observation they concluded that the innervated and contains large amounts of lymphatic 53 periosteum secreted bone.35 In the mid 1800s, vessels. It contains different types of nerves: sen- Dupuytren proposed that the cartilage of fracture sory and vasomotor nerves. These vasomotor nerves callus originated from periosteum and bone mar- regulate vessel tone by regulation of precapillary row.36 In 1867 Ollier proved that the deep cellular or sphincters and capillary blood flow. Pain fibres with osteogenic layer of a free periosteal graft is able to nociceptors are highly expressed which explains the 74 produce bone. This view was not disputed until in intense pain that follow periosteal injuries. 1912 when Sir W. Macewan published his work The Growth of Bone in which he described many experi- ments which seemed to demonstrate that the peri- Microscopic features osteum cannot be considered osteogenic, and that it must be viewed merely as a limiting membrane of Generally, periosteum is composed of an outer much the same nature as the sheath of a muscle or fibrous and inner cellular layers and does not the capsule of one of the viscera. This observation of supply epithelial cells, though periosteum has a periosteum as merely a limiting membrane was the potential to produce collagen.25 The structure confirmed by the Gallie and Robertson in 1914.44 of the periosteum in terms of ultrastructure and Then Lacroix in 1945 demonstrated the osteogenic functional organisation was not definitively under- capability of mature periosteum.65 stood until recently. The original division into two anatomical layers was made by Tonna in 1965, and only in 1986 Tang and Chai clearly delineated Anatomical considerations osteogenic cells of the cambium from fibroblasts (fibrous layer).124,128 The periosteum is specialised fibrous tissue in a form of fibro-vascular membrane. This well vascularised fibrous sheath, covers the external surface of most bones and is absent from articular surfaces, tendon insertions, or sesamoid bone surfaces.60 The peri- osteum and bones are bound together by collagen fibres called Sharpey’s fibres that penetrate into bone. The direction of collagen fibres is determined by tension forces (Fig. 1). These fibres penetrate entire cortex at the sites exposed to the high tension forces and the results are tight junctions of tendons and bones.136 In the region of the diaphyses of long bones the periosteum is thicker (2—3 mm) and easily separated from the underlying bone. It is strongly fused with bones in the metaphyseal and epiphyseal region where it is thinner. The main feature of children’s bone is to grow, Figure 1 Cortex (K), periosteum (P) and muscle (M). wrapped with elastic, firm periosteum. This explains Collagen fibres (Sharpey’s fibres, blue arrows) penetrate why childrens’ fractures have some specific biome- from periosteum to bone matrix. The periosteum 1117 Figure 2 The periosteum of sheep tibia. (a) Magnification 250Â and (b) magnification 25Â. Photomicrograph of normal periosteum attaching to bone. Periosteum consists of two clearly divided layers: osteogenic, cambium (K) and fibrous (F) layer. Periosteal surface (P) adjacent to the cortex. Microscopically (Fig. 2), the periosteum consists of analysis of periosteal morphology of the dog with an outer, fibrous, firm layer (collagen and reticular light and electron microscopy. fibres) and an inner, proliferative layer (cambium) Zone I consists mainly of osteoblasts arranged in which lies adjacent to bone and contains osteoblast the layer adjacent to the bone surface in a form of and osteoprogenitor cells (Fig. 3). Cambium is cap- simple epithelium and a supraosteoblast layer of able of: (a) forming normal lamellar bone apposition smaller,compact cells.6 Adjacent to primary (imma- on cortical bone that grows in width and (b) forming ture) bone, during intense synthesis of extracellular primary, woven bone after a fracture.54,103,124,129 matrix, osteoblasts are cuboidal, arranged as stra- The outer fibrous layer provides elasticity and flex- tified epithelium, with basophilic cytoplasm with ibility, whereas the inner cambium is the osteogenic high levels of alkaline phosphatase (Fig. 4).38 With layer and contains three or four cell layers, including the decrease of activity, osteoblasts elongate osteoblasts and preosteoblastic cells.24,27,119 and basophilic characteristics of the cytoplasm The first division of the periosteum into three decrease. The layer over the osteoblasts consists layers was made by Squier et al.119 in 1990 with the of small, spindle cells with scarce endoplasmic reti- Figure 3 Periosteal covering of the human femoral midshaft. Note the abundance of cells (arrowheads) near the periosteal surface comprising the cambium layer stained with Masson trichrome. Magnification 400Â, bar = 25 mm. From Ref. [3]. 1118 G. Augustin et al. Figure 4 Periosteum of the sheep tibia. Zone I: basophilic osteoprogenitor cells (red arrows) of germinative layer in transition to Zone II (blue line). Zone II: transparent zone with capillaries (yellow arrows) consists of extracellular matrix and fibroblasts. Magnification 25Â, bar = 15 mm. Hemalaun-eosin. Imunohistochemical staining with CD 31 and CD 34 (von Willenbrand factor). culum that are similar to fibroblasts. These are tially surround capillaries. Pericytes are found in the osteogenic progenitor cells which differentiate into microvasculature of connective tissue, nervous tis- osteoblasts. Fibrous tissue consists mainly of col- sue, muscle tissue and the lungs.115 These cells have lagen and small amount of elastic fibres.125 Fibro- the ability to contract and hence may regulate blood blasts are scarce and blood vessels are almost flow in the microvasculature.23 Pericytes may also completely lacking.114 This is the thinnest part of function as resting stem cells and differentiate into the periosteum (also called germinative layer). smooth muscle cells.81 They may also play a regu- Zone II is a relatively transparent zone with latory role in controlling capillary proliferation dur- capillaries and amorphous extracellular matrix mak- ing wound healing,31 and support capillaries in ing the most voluminous part (Figs. 5 and 6). The maintaining structural rigidity of the micro-vessel fibroblasts constitute most of the cellular compo- wall.29 Pericytes are cells in physical contact