Bone Structure and Physiology

Bone owes its properties to a composite of two main ingredients. The organic part is mostly type I collagen, which gives bone its tensile strength and a degree of flexibility, and the inorganic part is a calcium phosphate mineral called hydroxyapatite, which gives stiffness and resistance to compression. Together they make bone both strong and slightly springy, so it bends a little under load rather than shattering.

At the naked-eye level there are two forms of bone. Cortical, or compact, bone is dense and solid, forming the outer shell and the shafts of long bones, and it makes up most of the skeleton by weight. Trabecular, or cancellous, bone is the porous, honeycomb-like tissue found at the ends of long bones and inside the vertebrae; it has a large surface area, is more metabolically active and turns over faster than cortical bone. A typical long bone has a central shaft, the diaphysis, that flares into the metaphyses and then the epiphyses at each end, with the growth plate, or physis, sitting between them in the growing skeleton. The outer surface is wrapped in periosteum, the inner surfaces are lined by endosteum, and the hollow centre forms the medullary cavity.

Under the microscope, cortical bone is built from osteons, also called Haversian systems, which are concentric rings of bone laid down around a central canal carrying blood vessels and nerves. Trabecular bone is arranged instead as a lattice of interconnecting struts aligned along the lines of load. Throughout both, mature bone cells sit in tiny spaces within the matrix, linked to one another by fine channels that let them communicate.

Three main cell types keep bone alive and allow it to renew. Osteoblasts build bone, laying down new matrix that then mineralises. Osteocytes are former osteoblasts that have become trapped within the matrix they made; they form a vast connected network and act as the bone's mechanical sensors. Osteoclasts are large, multinucleated cells that resorb bone, dissolving the mineral and digesting the collagen matrix.

These cells work together in a continuous process called remodelling, which replaces old or damaged bone with new bone throughout life. The cycle runs in a set order: osteoclasts first resorb a small packet of old bone, a brief reversal phase follows, then osteoblasts move in to form new matrix, which finally mineralises. In healthy bone, resorption and formation are balanced, so bone mass is maintained.

The balance between resorption and formation is controlled largely by a signalling system built around three molecules. Osteoblast-lineage cells, and osteocytes in particular, produce receptor activator of nuclear factor kappa-B ligand (RANKL), which binds receptors on osteoclast precursors and drives them to mature into bone-resorbing osteoclasts, along with a decoy molecule, osteoprotegerin (OPG), that mops up RANKL and blocks osteoclast formation. The ratio of RANKL to osteoprotegerin therefore strongly influences osteoclast formation and resorption, and many of the hormones and drugs that affect bone act through this pathway.

Bone is also central to the control of blood calcium, holding the large reserve the body draws on to keep calcium within a narrow range. When blood calcium falls, parathyroid hormone is released and acts on bone to increase resorption indirectly, through signals from osteoblast-lineage cells to osteoclasts, releasing calcium into the blood. It also raises calcium reabsorption in the kidney and drives the kidney to activate vitamin D, which in turn increases calcium absorption from the gut. Vitamin D is needed for normal calcium absorption and mineralisation, and calcitonin has a lesser role opposing resorption.

Sex hormones matter greatly for the adult skeleton. Oestrogen restrains bone turnover, so when oestrogen levels fall, whether at the menopause or when hormonal function is suppressed, resorption speeds up and bone is lost. This is why hormonal disturbance is such an important influence on bone strength. Overall, bone strength depends not only on the amount of mineral present but also on the quality of the underlying architecture, so two bones with similar density can still differ in how well they resist load.

Bone constantly adapts to the mechanical demands placed on it, the principle known as Wolff's law. Osteocytes detect the strain produced by weight-bearing and by the pull of muscles, and signal for bone to be reinforced where loads are highest, so the skeleton becomes stronger and better shaped to resist the forces it meets. The reverse is also true: when load is removed, as in prolonged bed rest or spaceflight, bone is quickly lost.

Not all exercise loads bone equally. Weight-bearing, impact and progressive resistance activities provide a strong stimulus for bone formation, whereas non-weight-bearing activities such as swimming and cycling load the skeleton much less. Timing matters too, because most bone mass is accrued by late adolescence or early adulthood, with site-specific consolidation continuing into the third decade. The peak reached then, set by genetics, nutrition, loading and hormones, strongly influences bone strength for the rest of life, so weight-bearing exercise in youth helps build a higher peak and continued loading in adulthood helps maintain it.

This physiology runs through much of sport and exercise medicine. Because bone adapts to load, a sudden mismatch between training load and the bone's capacity to adapt can produce a bone stress injury, where repeated loading outstrips repair. The same biology explains why low energy availability, with endocrine disturbance that includes menstrual dysfunction in females and reduced reproductive hormone function in males in the picture of relative energy deficiency in sport (RED-S), weakens bone and raises injury risk, and why the fall in oestrogen with age drives bone loss. Supporting bone in athletes therefore rests on adequate loading, sufficient energy and nutrition including calcium and vitamin D, and attention to hormonal health.

• •Bone matrix combines type I collagen for tensile strength with hydroxyapatite mineral for stiffness.
• •Cortical bone forms the dense shell and shafts; trabecular bone is active and turns over faster.
• •Osteoblasts build bone, osteoclasts resorb it, and osteocytes sense mechanical load.
• •Remodelling order is resorption, reversal, formation, then mineralisation, set by the RANKL to osteoprotegerin ratio.
• •Bone adapts to load (Wolff's law), so weight-bearing and impact build it and unloading loses it.
• •Most bone mass is laid down by late adolescence or early adulthood.