What Is The Periosteum

The periosteum is a membranous tissue that forms the outer lining of bone tissue. Within the periosteum, bone progenitor cells and a host of growth factors are sequestered, making it a particularly important tissue for actively promoting bone growth, vascularisation, innervation and regeneration.¹ Although present in most bones, the periosteum is absent from sesamoid bones (small bones present within tendons or muscles which typically act as tensile pulleys. For example, the patella in the knee or the pisiform in the wrist). In long bones, the periosteum is located principally along the bone shaft and does not develop along the joint surfaces at the proximal and distal ends.²

Structure

Periosteum comprises two distinct layers. An outer fibrous layer and an inner cambium layer. The latter is so-called due to the noted parallel with trees by Duhamel in 1739 when he observed that silver wires placed under the periosteum resulted in the deposition of nascent bone matrix.² In plants, the cambium is a layer of tissue that houses undifferentiated cells and is responsible for co-localised plant growth and secondary thickening (formation of woody plants). The cambium also forms the distinct ring pattern in traverse cuts in trees.

The inner cambium layer of the periosteum contains undifferentiated cell types such as mesenchymal stem cells and osteoprogenitor cells. This layer is highly proliferative, playing a significant role in bone growth, healing or regeneration and the development of lamellar bone.³ The outer fibrous layer is comparably firmer and is made up of fibroblast cells embedded in a network of Sharpey’s fibres; bundles of type I collagen filaments set in calcified bone matrix that effectively act to anchor and co-localise the periosteum to the bone. It also imparts a degree of elasticity and integrity to the tertiary structure of the periosteum as a whole.

Bone homeostasis

Bone as a tissue type is dynamic, constantly undergoing deconstruction and remodelling by innate cell types such as osteoblasts and osteocytes. These changes accommodate the normal lifecycle as well as adaptive responses to changes in external factors that may have a direct impact on bone such as exercise or trauma for example. It is therefore not at all surprising that the periosteum forms part of this overall dynamism to maintain the overall integrity of bone tissue. Unlike the inner (endosteal) bone, the periosteum acts as a point of attachment for other musculoskeletal tissues such as fibrocartilage, tendon and ligaments and therefore experience very different shear and tensile forces. As a reflection of this, osteoblast cells within the periosteum behave differently from their counterparts in the endosteum. They are typically more sensitive to mechanical stimuli,⁴ are more resistant to changes in hormonal levels⁵, and produce higher quantities of the bone-specific protein periostin.⁶

The constitution of the periosteum can also be subjective within the skeletal framework of a mammal. The periosteum that lines the skull (calvarial bone) exhibits a distinct regulatory pattern from the bones which make up the core or axial skeleton (vertebrae, sacrum tailbone and rib cage), for example.³ There are also reported instances where the layers of the periosteum can vary along the length of a singular bone dependent on the cell density distribution along the bone itself.³ As part of the ageing process, the periosteum also loses some innate elasticity.³

Periosteal reactions to insult or injury – a diagnostic tool

Environmental stress such as injury, trauma, infection, disease and tumour development, which can cause sudden and extensive change or disruption in bone structure outside of normal bone cell remodelling activity can have a knock-on effect on cell activity in the periosteum. Changes in the periosteum are such that measured changes in the reaction to a ‘change of state’ can be detected by imaging techniques that can be used to support the diagnosis and determine the extent of damage that has occurred to a particular bone.⁷ In particular, radiological imaging techniques such as X-rays, computer tomography (CT), magnetic resonance imaging (MRI), ultrasounds and fluoroscopy are routinely used to ascertain periosteal reactions.

Periosteal reactions are broadly classified into aggressive, where bone deposition to the site of insult or injury has a fast turnover as a result of severe injury, infection or tumour malignancy. Or they are classified as non-aggressive, where the periosteal response is comparatively slower with a better response organisation for healing.⁷ Both aggressive and non-aggressive periosteal responses result in the typified regeneration patterns that allow physicians to make an assessment and diagnosis on imaging. A detailed overview of these patterns are reviewed in a publication by Alencar and colleagues and is summarised in Table 1.³

Clinical significance and tissue engineering applications

As a distinct tissue that possesses highly proliferative osteoprogenitor and mesenchymal stem cells, which possess distinct regulatory and osteogenic behaviour from their counterparts in the bone marrow. The periosteum is undoubtedly an important inspiration for tissue engineering and regenerative medicine applications. The observed differences in cellular responsiveness to physical, chemical and mechanical stimuli to periosteal progenitor cells hold significant potential for increasing the effectiveness and safety of therapies.

As the periosteum is not present in all bones, those without a periosteum adopt other methods for growth and maintenance.² Compared to cancellous bone, cortical bone is not rapidly vascularised and therefore bone regrowth can be considerably slower.⁸ Nonetheless, the use of bone allografts can be used to heal large defects in cortical bone and have shown much better success when compared to other available material implants such as ceramics or bone cement.⁸ 

Bone grafts, however, rely heavily on the osteointegrative ability of the grafted bone tissue, and the lack of sufficient growth factors and progenitor cells in a donor graft means that the healing process is often limited. Alternatively, the development and use of periosteal grafts and flaps can significantly increase the chances of successful bone integration and remodelling. This, in turn, has added patient benefits such as reduced healing time and a lessened risk of post-surgery infection.

Osteoporosis is a disease that is characterised by bone loss. Therapeutics targeted to treat osteoporosis act by promoting the deposition of new bone and/or inhibit bone resorption during remodelling. Although not fully understood, it has been noted that drugs used to treat osteoporosis increase bone density and strength correlate with an expansion of the periosteal lining along the bone.⁹ Furthering our understanding of the regulatory mechanism of these drugs can potentially shed light on engineering the periosteum as well as help develop improved therapies to treat bone diseases.

Summary

The periosteum is a fibrous membrane tissue that lines the outer surface of mammalian bones. Although ubiquitous, it is absent from sesamoid bones such as the patella and it typically does not cover any singular bone in its entirety. As an anchor point for connective tissue to bone, and possessing a high population of pre-osteogenitor cells, the periosteum plays an important role in maintaining bone homeostasis. Turnover in new bone matrix deposition by the periosteum can be notably triggered by external stimuli such as mechanical, shear and chemical changes brought on by insult, injury or disease to compensate for damage.

The periosteum’s high performance and capabilities for bone regrowth, compared to bone marrow derived progenitor cells, has made the periosteum a focus of interest in tissue engineering and regenerative medicine applications. Synthetically fabricated biomimics of periosteum has the potential to significantly improve the efficacy and success rate of surgical bone grafts and biomaterial scaffolds used to bridge bone for wound repair. In the short term, further research of the periosteum will help develop our understanding of not just the tissue membrane itself but how it influences musculoskeletal integrity as well as the development of clinical techniques. In the long term, there is also a consideration that the current socio-economic and patient disease burden can be appreciably reduced.