bone

bone Fairly early in the evolution of multicellular organisms it became an advantage to have a hard body component which could provide protection for soft tissues and a firm base against which contractile elements such as muscle could perform precise movements like those involved in locomotion or grasping. The hard component was often formed from calcium carbonate, as found in shellfish, but other durable defences were provided by chitin (a complex carbohydrate), in crustaceans and insects, and even silica, in the glass sponges.

Man and most vertebrates are characterized by an internal rather than an external skeleton. With the exception of the young animal and the cartilaginous fishes, the hardness is provided by calcium phosphate, laid down as crystalline hydroxyapatite on a template of collagen (a fibrous protein), forming bone. The collagen confers some elasticity. In man, bone also acts as the major reservoir for several elements such as calcium, phosphorus, magnesium, zinc, and sodium. The storage and release of at least the first three of these into the extracellular space is modified by hormones such as parathyroid hormone, calcitonin, and 1,25-dihydroxyvitamin D.

The longest bone is the femur (thigh bone), which accounts for a quarter of one's stature; the smallest bone is the stapes — one of the tiny ossicles in the middle ear which transmits the vibrations from the ear drum to the inner ear.

There are over 200 bones in the adult skeleton. They can be divided into two principal types: the long bones such as the femur, tibia, and humerus, which develop principally from within a cartilaginous framework, and the flat bones such as the skull, bones of the pelvis, and scapula, which develop within membranes of fibrous tissue.

Bone development and growth

X-rays can detect primary centres of bone formation (ossification) in the mid shaft of long bones from the end of the second month of intrauterine life. Secondary centres of ossification appear at the ends of these bones mostly at various times after birth and always earlier in females than males. Some secondary centres, however, such as in the lower end of the femur, occur before birth and this was used in the past as a indication of the maturity of a fetus; this had crucial forensic implications as it could determine whether or not a mother would be charged for concealing the birth of a viable infant.

Towards the ends of the long bones there are specialized discs of cartilage (epiphyseal plates) stretching across the entire bone. The cells in this area have a high rate of multiplication, and it is the major site of longitudinal growth in the juvenile bone. The rate of growth is greatest in infancy and around puberty, and growth ceases when the epiphyseal plate itself finally ossifies. It is over 200 years since the anatomist, John Hunter, showed that the mass and width of bone is increased by surface accretion from the periosteum — a tough fibrous layer covering the bone — rather than by internal expansion.

The ultimate bone length and mass is largely genetically determined and the average racial differences in bone mass exemplify this, with black people having a higher peak bone mass than white Caucasians and higher still than Asians. However this may be modified by general nutritional status — particularly calcium and protein intake — and by physical load bearing. There is evidence that the impact of such environmental influences may be greatest around the time of puberty, and unfortunately the lifestyle of the average teenager in present day Western society does not favour optimal bone development.

Premature arrest of growth at the epiphyseal plate will result in dwarfism. The cause may be genetic (as in achondroplasia), or environmental (as in severe illness or starvation).

Epiphyseal growth is most rapid at the wrists and shoulders in the upper limbs and at the knees in the lower limbs. The increased output of sex hormones at puberty provides a strong stimulus to accelerated bone growth for two or three years and then leads to epiphyseal closure — fusion with the shaft of the bone. Children with precocious puberty end up with stunted growth, whereas in eunuchs the epiphyses remain open and they become tall in their later teens. Pituitary growth hormone is the other hormone involved in bone growth.

All bone surfaces, with the exception of cartilaginous articular surfaces which form a joint with a neighbouring bone, are invested with the fibrous periosteum, which has osteogenic (bone-forming) potential. The flat bones ossify directly from such fibrous tissue rather than from intermediary cartilage. The skull is made up of several bones separated by very irregular interdigitating seams called sutures. This arrangement permits the necessary flexibility of the head during the birth process and after ossification is completed the sutures seal up progressively throughout adult life. Examination of the extent of suture union provides a means for assessing the age of an adult skeleton after death, whereas in a child this can be judged by which ossification centres are present and which epiphyses are fused.

Bone structure

About 80% of the skeleton consists of compact or ‘cortical’ bone which is extremely dense and resistant to trauma, and whose degree of hardness is exceeded in the body only by the enamel of the teeth. Such material forms the thick shafts of the long bones and the surface of all bones. It is perforated by microscopic channels; the Haversian canals (described by Havers, an English physician in the seventeenth century). Blood vessels pass through these canals, and bone cells are arranged concentrically around them. These cells, the osteocytes, have long extensions which pass down an interlocking network of canaliculi in the bone. This same network also allows nutrients, gases, and solutes to permeate the bone from the Haversian blood vessels.

The other 20% of bone forms a delicate, lacy honeycomb with a high surface-to-volume ratio. Cellular activity in this component (called trabecular or cancellous bone) is greater than in compact bone, and a variety of metabolic, hormonal, or physical stimuli on the cells renders it more labile. Trabecular bone is found principally in the bodies of the vertebrae, the ribs, the pelvis, and at the ends of the long bones. It contains the red bone marrow where the cellular components of the blood are manufactured. The remainder of the interior of bones — the medullary cavity — contains fat, and the proportion of fat to red marrow increases with age.

Metabolism and remodelling

Live adult bone is not a rigid inorganic framework. If it were, then like other crystalline structures it would be subject to frequent fatigue fractures as a result of the repetitive strains to which it is subjected. At millions of microscopic sites throughout the skeleton, bone is constantly being broken down and then remade in a cellular process first detailed in the mid twentieth century by an American orthopaedic surgeon, Harold Frost, and termed remodelling. At any site and in response to signals which are, as yet, poorly understood, the osteocytes permit access to the underlying bone by osteoclasts; these are specialized bone-resorbing cells derived from primitive cells in the marrow which also generate other types of phagocytes. These large, multinucleated cells dig small pits in the bone over a period of several days and are then replaced by bone-forming cells, the osteoblasts — which are derived from precursors of the fibrous-tissue-forming series. Osteoblasts synthesize fibres of the protein collagen and dispose them in a regular pattern determined in part by the direction of local strain forces. They also synthesize matrix mucopolysaccharide and direct the later mineralization of collagen with crystalline calcium phosphate. Active metabolites of vitamin D are required to allow adequate provision of both calcium and phosphate at those sites. The osteoblasts are ultimately trapped in the calcified matrix which they themselves have created, and become osteocytes. These cells appear to be able to communicate with each other throughout the bone; their elongated processes form close junctions with each other rather than being joined together.

Whatever the details, one end of a bone can interpret strain and chemical signals from the other. In healthy young adults the remodelling process is in balance, with as much new bone being synthesized as old bone removed. It also permits some adaptation of distribution of bone within a bone (or even within the skeleton) in response to changing physical or biochemical stimuli. Thus the disposition of bony trabeculae or cortical thickness is not haphazard but determined by mechanical and growth signals. Throughout the vertebrates there is a fairly constant ratio between the amount of bone required to cope with the largest forces normally encountered, and that required to deal with average gravitational demands. It is about three to one — for mice through to elephants.

Bone mass and ageing

A minimum regular stress is required simply to maintain your skeletal mass — you either use it or lose it — but the strains required to increase your bone mass significantly have to be substantially more than is customary for the individual concerned. Men have more bone than women at all ages because they are larger, but in both sexes bone mass (as measured conveniently by ‘dual energy X-ray densitometers’) increases into the third decade and plateaus from then till about the end of the fifth decade. It then declines, very slowly in men, but more rapidly in women for some years following the menopause. The average woman has lost around 20% of her peak bone mass by the time she is 70 years old (though estimates from different studies vary). This increases her risk of fractures and broken bones. The decline in bone mass in postmenopausal women can be reduced by taking oestrogen, and load-bearing exercise can increase bone mass to a modest extent in both men and women.

Any bone will fracture if it is subjected to sufficient force, but orthopaedic statistics reveal that over the past fifty years in the Western world there has been a striking rise in the incidence of certain fractures in older people, usually associated with only modest trauma. Fractures of the femoral neck (hip fracture), vertebral bodies (spine fracture), and wrist predominate, and appear to relate to populations having less bone at these sites. This condition, where reduced bone mass increases the liability to fracture, is called osteoporosis and represents one of our principal medical challenges today. In osteoporosis the remodelling process is not in equilibrium; less new bone is being formed than is being removed. It probably relates to several modern lifestyle changes affecting bone metabolism — notably diet and physical labour. The fact that Asian populations have smaller skeletons in any event and are adopting many of the same lifestyle features has led to predictions that hip fracture in that part of the world will become one of the greatest health care problems of the twenty-first century.

Several drugs are now available which have powerful actions on bone metabolism: examples are the bisphosphonates and the calcitonins, both of which inhibit bone resorption and can be used in the treatment of osteoporosis. The drug most commonly taken with such an effect is oestrogen, as hormone replacement therapy (HRT). It may also enhance bone formation.

The other common bone pathology is osteomalacia (called ‘rickets’ in children). In this disorder the bone is poorly mineralized, permitting softening and deformity such as bow legs. The usual cause is lack of vitamin D in the diet and/or lack of exposure to sunlight, and supplements of vitamin D are the appropriate treatment.

Ancient bones

Of all the body tissues, bone — apart from the teeth — is usually the only one to survive significantly beyond our mortal span. Ignoring palaeological niceties, some ‘human’ skeletons have been dated at around two million years old and provide us with much of the scanty evidence we have concerning the evolution of our species. Depending on the bones available, careful examination can allow reasonable inference concerning cranial development, height, and nutrition, in addition to the presence of diseases such as tuberculosis and leprosy and the medico-social practice of skull trepanning. The persistence of minute quantities of DNA within ancient bones may, by the application of sophisticated Polymerase Chain Reaction (PCR) augmentation and analysis, permit conclusions on the evolutionary/racial classification of some prehistoric skeletal remains. Look after your bones — they may tell your story long after you are gone!

Iain Boyle

Bibliography

Frost, H. M. (1964). Laws of bone structure. Thomas Springfield, Illinois.

See also calcium; hormone replacement therapy; joints; parathyroid glands; skeleton.