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Principles of Bone Healing Neurosurg Focus 10 (4):Article 1, 2001, Click here to return to Table of Contents Principles of bone healing IAIN H. KALFAS, M.D., F.A.C.S. Department of Neurosurgery, Section of Spinal Surgery, Cleveland Clinic Foundation, Cleveland, Ohio Our contemporary understanding of bone healing has evolved due to knowledge gleaned from a continuous interac- tion between basic laboratory investigations and clinical observations following procedures to augment healing of frac- tures, osseous defects, and unstable joints. The stages of bone healing parallel the early stages of bone development. The bone healing process is greatly influenced by a variety of systemic and local factors. A thorough understanding of the basic science of bone healing as well as the many factors that can affect it is critical to the management of a vari- ety of musculoskeletal disorders. In particular, the evolving management of spinal disorders can greatly benefit from the advancement of our understanding of the principles of bone healing. KEY WORDS • bone healing • spinal fusion • arthrodesis Bone is a dynamic biological tissue composed of meta- thick outer layer, termed the “fibrous layer,” consists of ir- bolically active cells that are integrated into a rigid frame- regular, dense connective tissue. A thinner, poorly defined work. The healing potential of bone, whether in a fracture inner layer called the “osteogenic layer” is made up of os- or fusion model, is influenced by a variety of biochem- teogenic cells. The endosteum is a single layer of osteo- ical, biomechanical, cellular, hormonal, and pathological genic cells lacking a fibrous component. mechanisms. A continuously occurring state of bone dep- Osteoblasts are mature, metabolically active, bone- osition, resorption, and remodeling facilitates the healing forming cells. They secrete osteoid, the unmineralized or- process. ganic matrix that subsequently undergoes mineralization, The success of many spine operations depends on the giving the bone its strength and rigidity. As their bone- restoration of long-term spinal stability. Whereas spinal forming activity nears completion, some osteoblasts are instrumentation devices may provide temporary support, a converted into osteocytes whereas others remain on the solid osseous union must be achieved to provide perma- periosteal or endosteal surfaces of bone as lining cells. Os- nent stability. The failure of fusion to occur may result in teoblasts also play a role in the activation of bone resorp- the fatigue and failure of supporting instrumentation and tion by osteoclasts. persistence or worsening of symptoms. Understanding Osteocytes are mature osteoblasts trapped within the the basic biological and physiological principles of bone bone matrix. From each osteocyte a network of cytoplas- transplantation and healing will aid the spine surgeon in mic processes extends through cylindrical canaliculi to selecting the most effective techniques to achieve success- blood vessels and other osteocytes. These cells are in- ful fusions. In this paper the anatomical, histological and volved in the control of extracellular concentration of cal- biological features of this process will be reviewed. cium and phosphorus, as well as in adaptive remodeling behavior via cell-to-cell interactions in response to local environment. BONE ANATOMY AND HISTOLOGY Osteoclasts are multinucleated, bone-resorbing cells The cellular components of bone consist of osteogen- controlled by hormonal and cellular mechanisms. These ic precursor cells, osteoblasts, osteoclasts, osteocytes, and cells function in groups termed “cutting cones” that at- the hematopoietic elements of bone marrow.10,22 Osteo- tach to bare bone surfaces and, by releasing hydrolytic progenitor cells are present on all nonresorptive bone sur- enzymes, dissolve the inorganic and organic matrices of faces, and they make up the deep layer of the periosteum, bone and calcified cartilage. This process results in the formation of shallow erosive pits on the bone surface which invests the outer surface of bone, and the endos- 12 teum, which lines the internal medullary surfaces. The called Howship lacunae. There are three primary types of bone: woven bone, periosteum is a tough, vascular layer of connective tissue 10,22 that covers the bone but not its articulating surfaces. The cortical bone, and cancellous bone. Woven bone is found during embryonic development, during fracture healing (callus formation), and in some pathological states Abbreviation used in this paper: BMP = bone morphogenetic such as hyperparathyroidism and Paget disease.22 It is protein. composed of randomly arranged collagen bundles and ir- Neurosurg. Focus / Volume 10 / April, 2001 1 Unauthenticated | Downloaded 10/01/21 02:58 PM UTC I. H. Kalfas regularly shaped vascular spaces lined with osteoblasts. Bone metabolism is also affected by a series of proteins, Woven bone is normally remodeled and replaced with cor- or growth factors, released from platelets, macrophages, tical or cancellous bone. and fibroblasts. These proteins cause healing bone to vas- Cortical bone, also called compact or lamellar bone, is cularize, solidify, incorporate, and function mechanically. remodeled from woven bone by means of vascular chan- They can induce mesenchymal-derived cells, such as mo- nels that invade the embryonic bone from its periosteal nocytes and fibroblasts, to migrate, proliferate, and differ- and endosteal surfaces. It forms the internal and external entiate into bone cells. The proteins that enhance bone tables of flat bones and the external surfaces of long healing include the BMPs, insulin-like growth factors, bones. The primary structural unit of cortical bone is an transforming growth factors, platelet derived growth fac- osteon, also known as a haversian system. Osteons consist tor, and fibroblast growth factor among others.18,32 of cylindrical shaped lamellar bone that surrounds longi- The most well known of these proteins are the BMPs, a tudinally oriented vascular channels called haversian ca- family of glycoproteins derived from bone matrix. Bone nals. Horizontally oriented canals (Volkmann canals) con- morphogenetic proteins induce mesenchymal cells to dif- nect adjacent osteons. The mechanical strength of cortical ferentiate into bone cells. Although typically present in bone depends on the tight packing of the osteons. only minute quantities in the body, several BMPs have Cancellous bone (trabecular bone) lies between cortical been synthesized using recombinant DNA technology and bone surfaces and consists of a network of honeycombed are currently undergoing clinical trials to assess their po- interstices containing hematopoietic elements and bony tential to facilitate bone fusion in humans.26–28 trabeculae. The trabeculae are predominantly oriented Other proteins influence bone healing in different ways. perpendicular to external forces to provide structural sup- Transforming growth factor–␤ regulates angiogenesis, port.16,29 Cancellous bone is continually undergoing re- bone formation, extracellular matrix synthesis, and con- modeling on the internal endosteal surfaces. trols cell-mediated activities. Osteonectin, fibronectin, os- teonectin, and osteocalcin promote cell attachment, facili- 15,20,22 BONE BIOCHEMISTRY tate cell migration, and activate cells. Bone is composed of organic and inorganic elements. By weight, bone is approximately 20% water.22 The weight PHYSIOLOGY OF BONE REPAIR AND FUSION of dry bone is made up of inorganic calcium phosphate The use of a bone graft for purposes of achieving ar- (65–70% of the weight) and an organic matrix of fibrous 10,19,21,22 throdesis is affected by each of the aforementioned ana- protein and collagen (30–35% of the weight). tomical, histological, and biochemical principles. Addi- Osteoid is the unmineralized organic matrix secreted tionally, several physiological properties of bone grafts by osteoblasts. It is composed of 90% type I collagen and directly affect the success or failure of graft incorporation. 10% ground substance, which consists of noncollagenous These properties are osteogenesis, osteoinduction, and os- proteins, glycoproteins, proteoglycans, peptides, carbohy- 20 20,22 teoconduction. drates, and lipids. The mineralization of osteoid by in- Osteogenesis is the ability of the graft to produce new organic mineral salts provides bone with its strength and rigidity. bone, and this process is dependent on the presence of live The inorganic content of bone consists primarily of cal- bone cells in the graft. Osteogenic graft materials contain cium phosphate and calcium carbonate, with small quan- viable cells with the ability to form bone (osteoprogenitor tities of magnesium, fluoride, and sodium. The mineral cells) or the potential to differentiate into bone-forming crystals form hydroxyapatite, which precipitates in an or- cells (inducible osteogenic precursor cells). These cells, derly arrangement around the collagen fibers of the oste- which participate in the early stages of the healing process oid. The initial calcification of osteoid typically occurs to unite the graft with the host bone, must be protected within a few days of secretion but is completed over the during the grafting procedure to ensure viability. Osteo- course of several months. genesis is a property found only in fresh autogenous bone and in bone marrow cells, although the authors of radiola- beling studies of graft cells have shown that very few of REGULATORS OF BONE METABOLISM these transplanted cells
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