Bone Composition and Structure

Where the rest of this lives. This page is the material - what bone is made of and how it is arranged. The cells that build and remove it have their own pages, osteoblasts and osteoclasts, and the cycle they run together is bone remodeling; the same matrix laid down again after injury is bone healing, and the organic phase in more detail is proteoglycans and collagen. The three diseases that read straight off this composition are worth holding together, because each fails a different component: osteogenesis imperfecta is defective type I collagen - too little normal matrix; osteomalacia is failure to mineralise a normal matrix; and osteoporosis is too little of an otherwise normal, normally mineralised bone. Same composite, three different points of failure.

What bone is. Bone is a specialised connective tissue doing four jobs at once: structural support, protection of vital organs, mineral homeostasis as the calcium and phosphate reservoir, and haematopoiesis in the marrow it encloses.

A composite material. By weight, bone is 65% inorganic mineral (hydroxyapatite), 25% organic matrix and 10% water. The mineral phase provides stiffness and compressive strength; type I collagen, which is 90% of the organic matrix, provides tensile strength and toughness.

The two demonstrations. Take the mineral out with acid and bone becomes flexible, bending like rubber. Take the collagen out with heat and it becomes brittle, shattering like chalk. Both components are needed for normal mechanical properties.

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The crystal. The mineral is hydroxyapatite, Ca10(PO4)6(OH)2, in hexagonal crystals of nanoscale dimensions: 50 nm long, 25 nm wide and only 2-3 nm thick. Crystal size and orientation are important to bone biomechanics.

Where the crystals sit. They are deposited within and between the collagen fibrils, aligned with the long axis of the fibril.

Ion substitutions. The apatite lattice tolerates ion exchange, and the substituting ion alters crystallinity and solubility, and through them mineral quality and remodelling dynamics.

Osteoid comes first. Osteoblasts secrete unmineralised organic matrix - osteoid - and mineral follows it after a lag of 10-14 days. At the mineralisation front that unmineralised layer is 10-15 micrometres thick.

What mineralisation needs. The process is tightly regulated by the osteoblast and requires adequate calcium, phosphate and vitamin D.

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The collagen molecule. Type I collagen is a triple helix of two alpha-1(I) chains and one alpha-2(I) chain, 300 nm long as the tropocollagen molecule and 1.5 nm in diameter. Its sequence is a Gly-X-Y repeat, with glycine at every third residue.

Assembly. Collagen is built in four steps:

1. Intracellular: procollagen synthesis and hydroxylation, which requires vitamin C
2. Extracellular: procollagen to tropocollagen, by cleavage of the N- and C-propeptides
3. Fibril formation: tropocollagen self-assembles into fibrils with a 67 nm periodicity
4. Crosslinking: lysyl oxidase creates covalent crosslinks - pyridinoline and deoxypyridinoline

The non-collagenous proteins. The remaining 10% of the organic matrix is a set of proteins that regulate mineralisation and cell-matrix interaction.

Osteocalcin is particularly important as a clinical marker. It is secreted by osteoblasts during bone formation and is vitamin K-dependent, through gamma-carboxylation of its glutamate residues.

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Crosslinks. Crosslink quality affects bone mechanical properties and fracture resistance. Enzymatic crosslinking is the normal route: lysyl oxidase converts lysine to allysine, forming the mature, stable pyridinoline (PYD) and deoxypyridinoline (DPD) crosslinks that increase tensile strength.

Non-enzymatic crosslinks. The advanced glycation end-products (AGEs) accumulate with ageing and with diabetes. They are brittle, they do not contribute to normal strength, and they are associated with reduced bone toughness.

Seven levels. The same material is organised on seven scales, from the molecule to the whole bone as an organ.

The structure adapts to load. The hierarchy is not static, and the osteocyte is the cell that makes it adapt. Osteocytes sit in lacunae connected by canaliculi - the lacunocanalicular network - and mechanical loading drives interstitial fluid flow and shear stress over their processes, which they transduce into biochemical signals, notably modulation of sclerostin, the SOST-gene product that normally inhibits bone formation.

Wolff's law and the mechanostat. This is the cellular basis of Wolff's law - form follows function, trabeculae aligning along principal stress trajectories - and of Frost's mechanostat. Below a lower strain threshold (disuse) net resorption occurs; within a physiological window bone mass is maintained; above an upper threshold (overload) modelling adds bone, while pathological overload causes microdamage.

What that framework explains. Disuse osteopenia, the periprosthetic bone loss of stress shielding, and exercise-induced bone gain are all consequences of the same osteocyte-driven feedback acting on the structures described here.

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Cortical (compact) bone is dense lamellar bone: 80% of skeletal mass but only 20% of the bone surface area, with a porosity of 5-10% and a remodelling rate of 3-5% per year. It forms the diaphyses of the long bones and the outer shell of every bone, and it is the tissue that provides mechanical strength and protection.

The osteon. Its structural unit is the osteon, or Haversian system, a cylinder 200-300 micrometres in diameter:

• A central Haversian canal carrying blood vessels and nerves
• 4-20 concentric lamellae wrapped around it
• Osteocyte lacunae and canaliculi between the lamellae
• A cement line at the outer boundary

Secondary osteons are the ones produced by remodelling, and each is surrounded by a cement line, also called a reversal line.

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Trabecular (cancellous, spongy) bone is the other 20% of skeletal mass, and it carries 80% of the bone surface area, at a porosity of 50-90% and a remodelling rate of 20-25% per year. It fills the vertebrae, the pelvis and the metaphyses of the long bones.

The struts. A network of interconnected trabeculae, each 50-300 micrometres thick, oriented along the lines of stress (Wolff's law), with marrow in the spaces between them.

How it behaves. Trabecular bone has a lower modulus than cortical bone and is anisotropic, its strength depending on the direction of loading. Its high surface-to-volume ratio makes it the more metabolically active tissue: it is the metabolic reserve, and it distributes the loads handed to it.

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Why the turnover rates matter. The higher remodelling rate of trabecular bone makes it more responsive to metabolic change, and also more vulnerable to resorptive disease.

The stress-strain curve. The composite composition produces the mechanical behaviour examiners ask about, starting with the curve itself: an initial linear elastic region, whose slope is the Young's modulus, then a yield point, then a plastic region before failure; the area under the curve is the energy absorbed, which is toughness.

The numbers. Cortical bone has a Young's modulus of roughly 17-20 GPa, far below steel at about 200 GPa. Trabecular bone is much lower, roughly 0.1-2 GPa, and depends steeply on density.

Anisotropy. Bone is strongest in compression and along the long (osteon) axis, weaker in tension and weakest in shear, which is why the skeleton is loaded preferentially in compression.

Viscoelasticity. Bone is strain-rate dependent: stiffer, stronger, and storing more energy at high loading rates. High-energy trauma therefore releases more energy and drives more comminution, while low-rate loading produces simpler patterns. In those terms, removing the mineral leaves a ductile, low-modulus material, and removing the collagen a stiff but brittle one.

Lamellar bone is the mature form: collagen fibres parallel within each lamella, and the orientation alternating between lamellae like plywood. The slow deposition is what allows that organisation.

Woven bone is laid down rapidly, with disorganised collagen orientation, and it is weaker and more flexible than lamellar bone. It is the bone of the fracture callus, and it is remodelled to lamellar bone over months.

Why composition explains fracture patterns. High-energy trauma overcomes both components at once, the mineral that carries compression and the collagen that carries tension. Osteoporotic bone has adequate mineral but poor microarchitecture.

Fracture healing. Woven bone forms first in the callus and is remodelled to lamellar bone over 12-18 months. Three things get in the way: smoking impairs collagen synthesis, vitamin D deficiency delays mineralisation, and NSAIDs may inhibit bone healing.

Surgical planning. Assess bone quality on the preoperative imaging, then read it into the construct:

• Cortical thickness guides plate selection
• Trabecular pattern influences screw trajectory
• Bone density affects implant choice
• Consider bone grafting for defects

A favourite examiner manoeuvre is to ask which structural component is at fault in a given metabolic bone disease. Mapping each disease to the affected component — mineral phase, organic (collagen) phase, mineralisation process, or architecture/remodelling — makes the differential systematic rather than a list to be memorised.

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Bone composition and structure is a basic-science topic that underpins the way every major examining body and society frames metabolic bone disease, fracture risk and implant fixation. The principles are universal; the way bone quality is assessed and acted upon varies by guideline and by resource setting.

Intrafibrillar versus extrafibrillar mineral. The relative contribution of mineral located within versus around the collagen fibrils to whole-bone mechanics remains debated. Atomistic modelling indicates that intrafibrillar mineral alone cannot account for whole-bone stiffness, which implies that extrafibrillar mineral is essential, but the exact partition and its biological control are unsettled.

Bone quality beyond BMD. DXA-measured BMD explains only part of fracture risk. How best to capture the "quality" contribution - collagen crosslinks, crystallinity, microdamage, microarchitecture - in routine practice is unresolved; the Trabecular Bone Score and HR-pQCT are surrogates, not direct measures.

Fluoride and strontium. Agents that alter the mineral phase increase measured density but historically gave disappointing or paradoxical fracture outcomes, strontium ranelate having been withdrawn in many regions over cardiovascular concerns. More mineral does not equal stronger bone.

Osteocalcin's systemic role. Beyond its established role as a bone-formation marker, undercarboxylated osteocalcin has been proposed as a hormone influencing glucose metabolism and other systems. The clinical significance in humans remains an area of active investigation and is not yet exam-established fact.