ACHONDROPLASIA

Achondroplasia is a congenital affection in which there is marked shortness of the limbs, with consequent dwarfing. It is of autosomal dominant inheritance but many cases arise from a fresh gene mutation.

Pathology. There is a failure of normal ossification in the long bones, which may be only half their normal length. Growth of the trunk is only slightly impaired.

Clinical features. Achondroplasia is apparent at birth, the child being strikingly dwarfed, with very short limbs that are out of proportion to the trunk: shortness is especially marked in the proximal segments of the limbs (Fig. 6.1). Adult achondroplasts are seldom more than 130 cm (4 feet 3 inches) in height. The hands are short and broad, the central three digits being divergent and of almost equal length (‘trident’ hand). The head is slightly larger than normal, with a bulging forehead and depressed nasal bridge. There is marked lumbar lordosis, often with thoracic kyphosis, which may occasionally lead to compression of the spinal cord. There is no mental impairment and life expectancy is usually normal.

Fig. 6.1 Achondroplasia, showing the typical features in a child. The dwarfing is due to shortness of the limbs, especially in their proximal segments; development of the trunk is but little impaired. Note the ‘trident’ hands.

Radiographic features. Apart from striking shortness of the limbs, there are characteristic changes in the pelvis, the inlet being widened from side to side but narrowed in the antero-posterior diameter, with notably small greater sciatic notches. The spinal canal is also narrowed in the antero-posterior diameter, which predisposes to spinal stenosis. The calvarium of the skull is large, but the base short.

Treatment. With improved techniques of leg lengthening, there may be increasing scope in the future for worthwhile gain in stature.

OSTEOGENESIS IMPERFECTA (Fragilitas ossium)

Osteogenesis imperfecta is a congenital and inheritable disorder – or more probably a heterogeneous group of disorders – in which the bones are abnormally soft and brittle, on account of defective collagen formation. In addition to the bones, other collagen-containing tissues such as teeth, skin, tendons, and ligaments may be abnormal. It is usually transmitted as an autosomal dominant, but in a severe variant of the disease the parents are normal and a fresh gene mutation or autosomal recessive inheritance is postulated.

Clinical features. In the worst cases, which occur sporadically rather than from inheritance and probably represent a distinct entity, the child is born with multiple fractures and does not survive. In the less severe examples fractures occur after birth, often from trivial violence. As many as fifty or more may be sustained in the first few years of life. The fractures unite readily, but in the more severe cases marked deformity often develops, either from malunion or from bending of the soft bones (Fig. 6.2), and such patients may be badly crippled. In the milder cases there is a tendency for fractures to occur less frequently in later life.

Fig. 6.2 Recent and old fractures of the bones of the upper limbs in an infant with osteogenesis imperfecta (fragilitas ossium).

Additional features, not always present, are a deep blue colouration of the sclerotics of the eyes, deafness from otosclerosis (which becomes worse in later life), and ligamentous laxity.

Treatment. Fractures are generally treated in the ordinary way, but in a severe case intramedullary nailing of affected long bones should be considered as a means of preventing crippling deformity and permitting earlier resumption of activity. Newer techniques have been developed with telescoping rods, to obviate the need for multiple operations. Protective appliances, such as walking calipers, may be required in older children and adults.

MULTIPLE HEREDITARY EXOSTOSES (Diaphyseal aclasis)

This is a congenital affection characterised by the formation of multiple exostoses (osteochondromata) at the metaphysial regions of the long bones. It is transmitted by an autosomal dominant mutant gene without any gender predisposition.

Pathology. The fault is in the epiphysial cartilage plate. Nests of cartilage cells become displaced and give rise to bony outgrowths, which are capped by proliferating cartilage. Growth of the exostoses may cease at skeletal maturity. These exostoses, or osteochondromata, constitute one type of benign bone tumour (p. 109). The number of outgrowths varies; often there are between ten and twenty, of varying size. In severe cases the process of remodelling by which a bone attains its normal adult shape is impaired, and there may be marked deformity, with reduction of longitudinal growth and consequent shortness of stature. Malignant change in the cartilaginous cap of one of the tumours can lead to the development of a chondrosarcoma (the lifetime risk is approximately 5%).

Clinical features. Usually the only symptoms and signs are those caused by the local swellings, or by their pressure effects. The patient is often of short stature, and there may be marked deformity of the limbs. Malignant change – often lethal – is suggested by rapid enlargement of one of the swellings in a patient, often at the age of skeletal maturity.

Radiographs show the bony outgrowths. In severe cases the bones are broad and ill modelled (Fig. 6.3).

Fig. 6.3 Diaphysial aclasis (multiple exostoses). A shows stunting of the upper end of the femur due to failure of the remodelling process that accompanies normal growth. Defective remodelling is a characteristic feature of the disease in its more severe forms. B shows typical exostoses (osteochondromata) projecting from femur and tibia. Such outgrowths are always directed away from the end of the bone.

Treatment. An outgrowth that is causing symptoms should be excised at its base and sent for routine histological examination to exclude any malignant change. Some deformities, particularly when they interfere with function, may require corrective osteotomies. Leg length discrepencies may also require correction, by either epiphyseal arrest or lengthening procedures.

MULTIPLE ENCHONDROMATOSIS (Dyschondroplasia; Ollier’s disease¹)

In dyschondroplasia masses of unossified cartilage persist within the metaphyses of certain long bones, and the growth of the bone is retarded. The condition becomes evident in childhood, but the cause is unknown. In contrast with multiple hereditary exostoses, just described, heredity plays no part.

Pathology. The fault is in the epiphysial cartilage plate. In this respect dyschondroplasia resembles multiple exostoses, but this is the only resemblance between them: in other respects they are entirely distinct. Nests of cartilage cells are displaced from the epiphysial plate into the metaphysis, where they persist as enchondromata.

Any bone formed in cartilage may be affected. The more rapidly growing ends of the femur and tibia (that is, the ends near the knee) and the small long bones of the hands and feet are particularly common sites. There is a tendency for the disorder to affect one side of the body predominantly, or even exclusively. When a major long bone is affected interference with growth at the epiphysial cartilage adjacent to the lesion may lead to serious shortening and distortion of the bone (Fig. 6.4A). When skeletal growth ceases the masses of cartilage may ossify. Rarely one of the tumours undergoes malignant change, to become a chondrosarcoma (p. 117).

Fig. 6.4 Multiple enchondromatosis (Ollier’s disease). A Masses of proliferating cartilage occupy the metaphyses of one tibia. Growth is retarded and uneven. The normal tibia is shown for comparison. B Multiple enchondromata in the metacarpals and phalanges.

Clinical and radiographic features. A limb affected by dyschondroplasia is usually short and may be markedly deformed. The hands may be grotesquely enlarged by multiple cartilaginous swellings or outgrowths. Radiographs show multiple areas of transradiance in the affected bones (Fig. 6.4).

Treatment. Osteotomy may be required to correct deformities resulting from uneven growth of bone. If there is marked discrepancy in the length of the lower limbs a leg equalisation procedure (p. 46) may be advisable. Lesions in the hand may be curetted and packed with bone chips.

PAGET’S DISEASE¹ (Osteitis deformans)

Paget’s disease of bone is a slowly progressive disorder of one or several bones. Affected bones are thickened and spongy, and show a tendency to bend. The disease is one of the commonest general affections of the skeleton. The cause is unknown. It has been suggested that infection with a slow virus of the paramyxovirus family may be responsible, on the evidence of inclusion bodies that have been found consistently in the osteoclasts of affected bones.

Pathology. The basic abnormality is thought to be defective function of osteoclasts, with consequent irregular bone resorption and increase of bone turnover. The bones most commonly affected are the pelvis, vertebrae, femur, tibia, and skull. The disease may be confined to a single bone at first, but it often spreads to involve other bones later. The cortex of the bone loses its normal compact density and becomes spongy. At the same time the cortex is widened by the formation of new bone on both its outer and inner surfaces. The whole bone is thus thickened, but the usual sharp distinction between cortex and medulla is blurred. The marrow spaces are filled with fibrous tissue. Whereas the bone is soft and vascular at first, in the later stages there is a tendency for it to become denser and very hard.

In the spongy state the softened bones are liable to bend. Pathological fracture may occur. In rare instances osteosarcoma develops in the diseased bone.

Clinical features. The affection seldom begins before the age of 40, but a childhood form is recognised. Often there are no symptoms, the condition being discovered incidentally during routine radiographic examination. When long bones are affected pain is sometimes complained of, but it is by no means an invariable feature. Bending of the softened long bones leads to deformity, usually in the form of anterior and lateral bowing of the femur or tibia (Fig. 6.5). Thickening may be obvious clinically, especially in the case of the tibia or the skull. Thus if the patient wears a hat he may notice that he requires progressively larger sizes. More importantly, bone thickening may also cause constriction of foramina in the skull, with risk of damage to a nerve – for instance the optic nerve or the auditory nerve.

Fig. 6.5 (left) The typical appearance of a patient with widespread Paget’s disease. Note the bowing of the legs and shortening of the trunk from collapse of softened vertebrae. The head was also enlarged.

Imaging. The main radiographic features (Figs 6.6 and 6.7) are:

Fig. 6.6 (right) Paget’s disease. A Tibia, showing bending, coarsening of trabeculae, and thickened cortex which, however, is not sharply demarcated from the medulla. B Femur, showing broadening of the bone with loss of the normal demarcation of cortex and medulla.

Fig. 6.7 Paget’s disease. Half pelvis, side by side with a normal one shown for comparison. Note the coarse trabeculae and slight distortion of the softened pelvic ring, with deepening of the acetabulum.

The long bones are often shown to be bowed, the pelvis may be deformed, the vertebrae may be compressed and the vault of the skull thickened. Radioisotope scanning with ^99mtechnetium shows markedly increased uptake in the affected bones.

Investigations. The alkaline phosphatase content of the plasma is increased, often to a high level if several bones are affected. Urinary hydroxyproline is increased, reflecting the increased resorption of bone matrix.

Complications. The important complications are pathological fracture, compression of cranial nerves, and occasionally – but most importantly – osteosarcoma.

Treatment. Very often treatment is not required because the disability is negligible. Treatment is needed mainly for bone pain and for complications. Two drugs are known to affect the outcome – calcitonin and bisphosphonates.

Both drugs inhibit bone resorption. They reduce bone turnover, with lowering of plasma alkaline phosphatase, and both are effective in relieving bone pain in a high proportion of cases. Treatment must, however, be prolonged. Unlike calcitonin, which must be injected (though nasal spray and suppository forms are being tried), a bisphosphonate compound may be taken by mouth. Moreover its benefit often persists for up to six months after the drug has been discontinued; so it is the preferred drug in the first instance, on the basis of cost and ease of administration.

POLYOSTOTIC FIBROUS DYSPLASIA

Replacement of bone by fibrous tissue forms a conspicuous part of several unrelated bone diseases. In two conditions in particular, fibrous replacement is the predominant change. In one of these – parathyroid osteodystrophy – the changes are associated with hyperparathyroidism (p. 73). In the other, now to be described, there is fibrous replacement without any evidence of excessive parathyroid secretion.

Polyostotic fibrous dysplasia, then, is a condition in which parts of several bones are replaced by masses of fibrous tissue, but in which there is no evidence of hyperparathyroidism. The condition is rare and the cause is unknown. There is no evidence to suggest a genetic basis.

Pathology. The number of bones involved varies from two or three to twelve or more. The major long bones are those mainly affected – especially the femur. The skull and mandible are also commonly involved. Affected bones are liable to bend or break.

Clinical features. The onset is in childhood but the condition is often not recognised until adult life. The main features are deformity, from bending or local enlargement of bone, and pathological fracture. The disease progresses for years and may eventually lead to severe crippling.

Radiographs of the affected bones show well-defined transradiant areas which often have a characteristic homogeneous or ‘ground-glass’ appearance: these changes may be localised and patchy rather than uniform. The lesions are in the shaft and metaphyses rather than the epiphyses. When the lesion is extensive the cortex is expanded and thin, and the bone is bent when weight-bearing, producing deformities such as the ‘shepherd’s crook’ in the proximal femur (Fig. 6.8). Sometimes the lesion has a honeycombed appearance.

Fig. 6.8 Polyostotic fibrous dysplasia affecting the radius A and the tibia B. Parts of the skeleton are replaced by fibrous tissue, giving in places a ‘ground-glass’ appearance. Unlike hyperparathyroidism, this disorder is not associated with any known endocrine dysfunction. C Extensive fibrous dysplasia affecting the proximal femur with softening of the bone resulting in a typical ‘shepherd’s crook’ deformity.

Investigations. There is no consistent biochemical abnormality of the blood. In a few cases the plasma alkaline phosphatase has been raised.

NEUROFIBROMATOSIS (von Recklinghausen’s disease¹)

This is a congenital inheritable affection characterised by pigmented areas on the skin, cutaneous fibromata, and multiple neurofibromata in the course of the cranial or peripheral nerves. It is ascribed to an autosomal dominant mutant gene.

Pathology. The neurofibromata consist of connective tissue arranged in whorls, with a few nerve fibres.

Clinical features. Skin lesions are seldom present at birth but often develop in early childhood. They consist of multiple ‘café au lait’ areas, axillary or perineal freckling and of small fibromata which may be flat or raised. Neurofibromata may occur on any of the cranial or peripheral nerves, and important pressure effects may occur, including compression of the spinal cord.

The orthopaedic significance of neurofibromatosis lies mainly in the liability to scoliosis and to neurological disturbances in the limbs. There may also be pathological fracture – usually of the tibia in infants, due to fibrous infiltration of the bone (congenital pseudarthrosis).

Scoliosis. Why scoliosis should occur is unknown: but it is a common complication and it sometimes progresses to an angulation so severe that the function of the spinal cord is impaired.

Neurological disturbances. There may be impairment of function of cranial or peripheral nerves in consequence of neurofibromata lying in the course of nerve trunks. Various manifestations are observed, depending upon the site of the tumour. For instance, a tumour of a nerve root within the spinal canal may compress the spinal cord and give the typical picture of a spinal cord tumour. Or it may compress the cauda equina or an individual nerve trunk, with consequent radiating pain and impairment of function of the involved nerve. Thus neurofibromatosis enters into the differential diagnosis of brachial pain and sciatica.

Imaging. Plain radiographs may show erosion of a bone where a neurofibroma lies in contact with it. CT or MR scanning may be helpful in outlining the extent of a bulky neurofibroma.

Diagnosis. The pigmented spots or areas, and cutaneous fibromata, afford important clues to the diagnosis. A positive family history is important corroborative evidence.

Complications. Occasionally a neurofibroma may undergo malignant change, to become a neurofibrosarcoma.

Treatment. A neurofibroma that is causing symptoms should be excised.

MYOSITIS OSSIFICANS PROGRESSIVA (Fibrodysplasia ossificans)

Myositis ossificans progressiva is a congenital affection characterised by the formation of masses of bone in the soft tissues, with consequent progressive impairment of movement of the underlying joint or joints. It is often associated with shortness of the great toe or of other digits (microdactyly). Most cases are sporadic. It is caused by a defect in a gene for the receptor of the BMP family of proteins.

Pathology.¹ The ectopic bone is formed by metaplasia of connective-tissue cells, not from displaced osteoblasts.

Clinical features. Changes usually appear first in early childhood. Swellings develop in the region of the neck and trunk. At first soft and perhaps transient, they later give place to hard plates of bone which lie in the course of muscles, ligaments and fasciae. Movements of the spine and ribs, and later of the limb joints, are reduced progressively until in the worst cases there may be total immobility. In most cases the great toe is congenitally short; the thumbs or other digits may also be short.

Radiographs show the plates of bone in the soft tissues.

Progress. After many years increasing rigidity renders the patients bedridden. No curative treatment is known. Systemic treatment by bisphosphonates after excision of bony bars may retard their regeneration, but the eventual fatal outcome seems unlikely to be influenced significantly.

CRANIO-CLEIDO DYSOSTOSIS

In this dysplasia the most striking features are enlargement of the frontal and parietal regions of the head with delayed ossification and delayed fusion of the skull bones, and absence or partial absence of the clavicles. Other bones may also show less striking anomalies. The disorder is of autosomal dominant inheritance. It is caused by a mutation in the gene for osteoblast specific transcription factor 2 (osf 2) also known as (bfa-1) on chromosome 6.

Clinical features. The disorder usually becomes apparent in early childhood. The head is somewhat larger than normal, with bulging frontal and parietal regions. The clavicles are either absent or rudimentary, in consequence of which the two shoulders can be approximated anteriorly – a characteristic feature. Life expectancy is normal.

Radiographs in childhood show delayed fusion of the skull bones, with Wormian bones in the suture lines; absence of the clavicles either in whole or in the lateral parts; and delayed ossification of the pelvic bones with wide symphysis pubis.

GAUCHER’S DISEASE

Gaucher’s disease is one of the group of lysosomal storage diseases included under the generic title mucopolysaccharidoses or sphingolipidoses. It is a rare lipoid storage disease of autosomal recessive inheritance, in which the enzyme beta-glucosidase is deficient and gluco-cerebroside accumulates in reticulo-endothelial cells of the spleen, liver, bone marrow, and other tissues.

Clinical features. Symptoms usually appear first in adult life. There is enlargement of the spleen and liver. There may be a feeling of weakness due to anaemia, but often the general health is good. Skeletal involvement, which takes the form of infiltration and replacement of bone by masses of lipoid-laden reticulo-endothelial cells (Gaucher cells) brings a risk of pathological fracture. Bone pain or joint pain is a common feature.

Radiographs show irregular cyst-like spaces in some of the bones, sometimes with expansion of the cortex, especially of the femur, the lower end of which may appear flask-shaped. Osteonecrosis (avascular necrosis) of the head of the femur or the head of the humerus, with consequent disorganisation of the corresponding joint, is also common.

Investigations. Bone marrow biopsy usually yields typical Gaucher cells.

Treatment. Replacement therapy with the enzyme (glucocerebrosidase) is effective but very expensive. Splenectomy relieves local discomfort and may help the anaemia but it does not influence the chronic course of the disease.

HISTIOCYTOSIS X (Skeletal granulomatosis)

The title histiocytosis X comprises a group of diseases characterised by proliferation of histiocytes and storage within them of cholesterol. The three clinical entities to be briefly described are:

All occur mostly in children or young adults.

HYPERPARATHYROIDISM (Parathyroid osteodystrophy; generalised osteitis fibrosa cystica; von Recklinghausen’s disease)

The characteristic features of hyperparathyroidism are lassitude, dyspepsia, generalised osteoporosis, and cystic changes in some of the bones.

Cause. It is caused by excessive parathyroid secretion, usually from an adenoma of one of the parathyroid glands.

Pathology. The excessive secretion of parathormone causes generalised absorption of bone, the calcium from which is liberated into the blood, whence it is excreted in excessive quantities in the urine. The bone becomes spongy and the cortices are increasingly thin. Cystic changes often develop in one or more of the long bones: from their macroscopic appearance these are commonly referred to as brown cysts. A consequence of the increased excretion of calcium is that the kidneys frequently contain calculi.

Clinical features. The patient is adult. There are pains in the bones, indigestion, and weakness. There may also be deformity from bending of softened bone, or a pathological fracture.

Radiographic features. Radiographs show rarefaction of the whole skeleton. The loss of density may be marked, and the cortices very thin. An early sign is irregular subperiosteal cortical erosion in the phalanges of the fingers. Scattered cystic changes may be present in the long bones (Fig. 6.9A, B). The skull shows a uniform fine granular mottling, sometimes with small translucent cyst-like areas (Fig. 6.9C). Radiographs of the renal tracts often show nephrolithiasis.

Fig. 6.9 Hyperparathyroidism. A and B Radiographs showing the typical changes in the long bones: diffuse osteoporosis with marked thinning of the cortex and scattered fibrocystic changes (pathologically, ‘brown’ cysts). C The skull is fuzzy and finely mottled.

Investigations. The plasma calcium is increased but the plasma inorganic phosphate is diminished. Excretion of calcium and phosphate in the urine is increased.

Diagnosis. This is from other causes of diffuse or generalised rarefaction of bone. These are summarised in Table 6.1.

Treatment. The causative parathyroid tumour should be located and removed.

NUTRITIONAL RICKETS

In rickets there is defective calcification of growing bone¹ in consequence of a disturbed calcium–phosphate metabolism. With the general improvement in economic conditions infantile rickets has become rare in Western countries. There is, however, a relatively higher incidence among immigrants from the West Indies and from Asia.

Cause. Nutritional rickets is caused by a deficiency of vitamin D in the diet and by inadequate exposure to sunlight, which promotes the synthesis of vitamin D in the body.

Pathology. Vitamin D promotes the absorption of calcium and phosphorus from the intestine. Its deficiency therefore leads to inadequate absorption of calcium and phosphorus. The level of calcium in the blood can then be maintained only at the expense of the skeletal calcium. Proliferating osteoid tissue in the growing epiphyses remains uncalcified, and there is a general softening of the bones already formed (Fig. 6.10).

Fig. 6.10 Rickets. Note the typical widening and ‘cupping’ of the metaphyses of the radius and ulna. The depth of the epiphysial cartilage is increased, and the general density of the bones is reduced.

Clinical features. The ordinary nutritional rickets usually occurs in children about one year old. The general health is impaired. The predominant signs are a large head, retarded skeletal growth, enlarged epiphyses, curvature of long bones, and deformity of the chest, which may show a transverse sulcus. In a typical case these signs produce an easily recognised clinical picture.

Radiographic features. There is a general loss of density of the skeleton with thinning of the cortices. The most striking changes, however, are in the growing epiphyses. The vertical depth of the epiphysial lines is increased, the epiphyses are widened laterally, and the ends of the shafts are hollowed out or ‘cupped’ (Fig. 6.10). Bending of the bones may be obvious.

Investigations. The plasma phosphate level is usually decreased. The plasma calcium is normal. The alkaline phosphatase is increased, often markedly: its level gives some indication of the severity of the disease and of the response to treatment. Measurement of the serum levels of 25-hydroxyvitamin D is a useful guide to diagnosis and treatment.

Diagnosis. If rickets is suspected an antero-posterior radiograph of a wrist should be obtained. The radiographic features are diagnostic of rickets, but biochemical examinations are required to indicate its type (Table 6.2, p. 77).

Treatment. Nutritional rickets responds well to vitamin D in ordinary doses. Severe bony deformity persisting after vitamin therapy should be corrected by osteotomy or osteoclasis.

OTHER FORMS OF RICKETS

The characteristic epiphysial changes seen in nutritional rickets occur in a number of other diseases, the primary factor responsible for the disordered calcium–phosphate metabolism being different in each type. Four types will be described: familial hypophosphataemia, cystinosis, uraemic osteodystrophy, and coeliac (gluten-induced) rickets.

Uraemic osteodystrophy (renal osteodystrophy; renal (glomerular) rickets; renal dwarfism)

In uraemic osteodystrophy general skeletal changes are associated with chronic renal impairment. The skeletal changes often become manifest between the ages of 5 and 10 years.

Pathology. The renal impairment may be due to congenital cystic changes, to ureteric obstruction with hydronephrosis, or to chronic nephritis. The mechanism by which the renal deficiency leads to rachitic changes in the skeleton is uncertain, and probably complex. One factor may be that impaired excretion of phosphorus by the kidneys leads to retention of phosphorus in the blood, and its excretion in the intestine. There it forms an insoluble compound with calcium, which in consequence is not absorbed in proper amounts.

The skeletal changes consist in deficient epiphysial growth and multiple deformities from bone softening. The parathyroid glands are hypertrophied, probably as a secondary effect.

Clinical features. The child is dwarfed and deformed. There are symptoms of renal impairment, such as excessive thirst and sallow complexion. The common skeletal deformities are coxa vara, genu valgum, and severe valgus deformity of the feet.

Radiographs show epiphysial changes that are generally similar to those of nutritional rickets (Fig. 6.11).

Fig. 6.11 Rachitic changes in the epiphyses of a renal dwarf aged 14 years. There was diffuse rarefaction of the skeleton, with multiple deformities from bending of softened bones.

Investigations. The biochemical changes are characteristic (Table 6.2). The plasma phosphate is markedly increased. The plasma calcium is low. The blood urea is raised, often to a high figure. Albumin is usually present in the urine.

Prognosis. Unless the renal lesion is remediable gradual progression is likely, with poor prognosis.

Treatment. This should be directed primarily against the underlying renal condition. The diet should be supplemented with calcium and vitamin D.

NUTRITIONAL OSTEOMALACIA

Nutritional osteomalacia is the adult counterpart of infantile (nutritional) rickets. It is regarded as rare except in certain Asiatic countries. Nevertheless it may be more common than is generally realised, especially in elderly women.

Cause and pathology. As in infantile rickets, there is a deficiency of vitamin D (and often of calcium) in the diet. In consequence the intestinal absorption of calcium and phosphorus is inadequate, and calcium is withdrawn from the bones to maintain a reasonable level in the blood. The bone trabeculae are not abnormally thin, but they are largely composed of poorly calcified osteoid tissue. There is an abundance of fibrous tissue in the marrow.

Clinical features. The main features are pain in the bones, and deformity. Because of the porosity of the bones fractures are common.

Radiographic features. There is rarefaction of the whole skeleton. The bone cortices are abnormally thin. The long bones may be curved and the pelvis triradiate. Multiple spontaneous fractures (Looser’s zones), seemingly ununited though possibly bridged by unmineralised osteoid tissue, may be shown in ribs, pelvic rami, or elsewhere. These are characteristic of osteomalacia and are not seen in osteoporosis.

Investigations. The plasma calcium is normal or low. Plasma phosphate is low. Alkaline phosphatase is increased. The calcium balance is negative (Table 6.2, p. 77). Serum levels of 25-hydroxyvitamin D are low.

Diagnosis. Nutritional osteomalacia must be distinguished from other causes of diffuse rarefaction of bone (Table 6.1, p. 74). In the elderly it may be mistaken for idiopathic osteoporosis.

Treatment. Recalcification of the skeleton is induced by adequate diet and administration of vitamin D and calcium. Osteotomy may be required to correct deformity.

OTHER FORMS OF OSTEOMALACIA

Just as in children rachitic changes in the bones may occur from a number of different metabolic faults, so in adults osteomalacia may arise from causes other than purely nutritional. Such causes include advanced renal disease, and malabsorption syndromes such as chronic obstruction of the bile ducts, chronic pancreatic disease, and adult coeliac disease.

VITAMIN C DEFICIENCY (Infantile scurvy)

Scurvy is a haemorrhagic disease caused by a deficiency of vitamin C (ascorbic acid) in the diet. It is rare in Western countries, especially in adults.

Pathology. The most striking changes are in the long bones. There is a lack of osteoblastic activity in the epiphysial growth cartilage (growth plate). Haemorrhage, beginning at the epiphysial cartilage, extends beneath the periosteum, which may be raised from the bone throughout its whole length. Haemorrhages also occur from other sites, especially from the gums or within the orbit.

Clinical features. Scurvy affects infants during the second six months of life if the diet is deficient in fresh milk or other sources of vitamin C. The onset is rapid, with loss of use of a limb or limbs because of pain (pseudoparalysis). An affected limb is swollen and exquisitely tender over the affected bone or bones. The gums are often spongy and bleed, and there may be a ‘black’ eye.

Radiographic features. Plain radiographs show a dense line at the junction between metaphysis and epiphysial cartilage, with a clear band of rarefaction on the diaphysial side (Fig. 6.12A). Later there is ossification in the subperiosteal haematoma, as a result of which the bone is often markedly thickened (Fig. 6.12B).

Fig. 6.12 Infantile scurvy. A Early active stage. Note the clear zone in the metaphysis, indicating arrest of osteoblastic activity, and the dense zone adjacent to the epiphysial cartilage. B Later stage, showing well-marked ossification in the subperiosteal haematoma.

Investigations. Ascorbic acid is deficient in the plasma.

Diagnosis. The skeletal features of scurvy in infants resemble those of syphilitic metaphysitis, which, however, occurs at an earlier age – namely during the first 6 months of life. Other distinctive features are the positive Wassermann reaction in syphilis and bleeding from the gums in scurvy. Scurvy may also be confused clinically with acute osteomyelitis. Deficiency of plasma ascorbic acid is diagnostic.

Treatment. The disease responds readily to the administration of vitamin C.

OSTEOPOROSIS (Idiopathic osteoporosis; post-menopausal osteoporosis)

This condition is characterised by diffuse osteoporosis of unknown cause. It affects the elderly, especially post-menopausal women, but it may be seen also in patients of middle age. It may possibly have an endocrine basis.

Pathology. The whole skeleton is affected, but the changes in the spine are more obvious than those elsewhere. The cortices of the vertebrae are thinner than normal, and the bone is rarefied throughout from thinning of the individual trabeculae and widening of the vascular canals. In other words there is a reduction of total bone mass. Compression fracture of one or more of the vertebral bodies is liable to occur from only trivial violence. Even without fracture the thoracic vertebrae tend gradually to become wedge-shaped so that the spine bends forward to produce a rounded kyphosis. The long bones – particularly the upper end of the femur and the lower end of the radius – are also prone to fracture easily.

Clinical features. The patient is often a woman of over 60. The osteoporosis may be symptomless and may be found only by chance. In other cases there is pain in the back. The pain occurs in two forms – a mild generalised ache, and a sharper pain of sudden onset, denoting a compression fracture. Examination reveals a rounded kyphosis in the thoracic region. If a vertebral body has collapsed there may be a more angular kyphosis with prominence of a spinous process in the thoracic or thoraco-lumbar region. The trunk is shortened, with consequent loss of height, and there is a transverse furrow across the abdomen (Fig. 6.13A).

Fig. 6.13 Idiopathic osteoporosis. Note the rounded kyphosis and the shortened trunk with transverse furrow across the abdomen A. The radiograph B shows marked loss of density, with thinning of the cortices. The intervertebral discs are ballooned into the concave vertebral surfaces. Several vertebral bodies have collapsed. Differential diagnosis was from parathyroid osteodystrophy, osteomalacia, myelomatosis, diffuse carcinomatous deposits, and leukaemia.

Radiographic features. The striking feature is the reduced density of the vertebral bodies, which become concave at their upper and lower surfaces from pressure of the intervertebral discs. Often there is wedging of one or more of the vertebral bodies from compression fracture (Fig. 6.13B). Other parts of the skeleton are also rarefied, but less obviously.

Investigations. The biochemistry of the blood is normal. Metabolic balance studies may show a negative calcium balance. Bone density is best measured by dual X-ray absorptiometry.

Diagnosis. Osteoporosis may be confused with other forms of diffuse rarefaction of bone, especially that caused by parathyroid osteodystrophy, glucocorticoid excess (Cushing’s syndrome), osteomalacia of various types, carcinomatosis, myelomatosis, or leukaemia (Table 6.1, p. 74). Diagnosis rests largely on the exclusion of these specific disorders.

Prevention. Hormone replacement therapy (HRT) with oestrogens, supplemented by progesterone for 10 days of the month unless the patient has had a hysterectomy, is an important option in post-menopausal women.

Treatment. Once osteoporosis is established, treatment is rather unsatisfactory. It may be possible to restore the patient to positive calcium balance by high-dosage calcium supplements to the diet, combined with calcitriol if malabsorption is present; but the gain is slow because of the slow turnover rate of bone tissue. Thus a dramatic improvement in the radiographic appearance cannot be expected.

A number of drugs have been used in trials to treat established osteoporosis in the older patient, particularly after vertebral or femoral neck fractures. These are selected for their ability to decrease osteoclastic bone resorption or to stimulate the formation of new bone by osteoblasts. The most widely used inhibitors of bone resorption are bisphosphonates, while strontium and the peptide of parathyroid hormone may promote new bone formation.

HYPOPITUITARISM

Deficient secretion of the anterior lobe of the pituitary gland leads to various types of disturbance of skeletal growth, often with impairment of sexual development and sometimes with learning disabilities. The patient may be dwarfed, or on the other hand there may be good stature with marked obesity. The orthopaedic importance of this latter condition is that it may predispose to slipping of the upper femoral epiphyses in adolescents (p. 371) – as indeed may obesity from any cause.

GIGANTISM

In gigantism (one form of hyperpituitarism) skeletal overgrowth is caused by an excess of anterior pituitary hormone occurring before the growth epiphyses have fused.

Pathology. There is an eosinophilic adenoma of the anterior lobe of the pituitary. Excessive growth occurs at the epiphysial cartilages. Despite this over-activity, epiphysial fusion occurs at about the normal time.

Clinical features. The patient, usually a boy, may grow to a height of 7 feet or more, the main increase being in the limbs. Sexual development is often impaired and the mentality may be subnormal. Signs of acromegaly often develop later. Most of the giants, whose skeletons are preserved in medical museums, some more than 9 feet tall, are examples of this condition.

Diagnosis and treatment are as for acromegaly (see below).

ACROMEGALY

The primary fault is the same as in gigantism – namely, an excessive secretion of pituitary growth hormone – but it occurs after the epiphyses have fused. It is characterised by enlargement of the bones, especially of the hands, feet, skull, and mandible.

Pathology. As in gigantism, there is usually an eosinophilic adenoma of the anterior lobe of the pituitary. The enlargement of the bones is caused by deposition of new bone upon the surface of the original cortex.

Clinical features. The disease often begins in early adult life. The physical features become coarse and heavy, the skin is thickened, and the hands and feet slowly enlarge. At first strong, the patient often becomes weak and sluggish later. Radiographs show marked enlargement of the bones of the hands and feet, and especially of the mandible. The vertebral bodies are also enlarged, especially in the antero-posterior diameter. The sella turcica of the skull may be expanded and eroded.

Diagnosis. This is made from the clinical appearance and by demonstration of excessive growth hormone excretion by radio-immunoassay.

Treatment. Early treatment – often by removal of the pituitary adenoma or sometimes by irradiation or by drug therapy – is important in preventing deterioration.

INFANTILE HYPOTHYROIDISM (Cretinism)

Infantile hypothyroidism (cretinism) is characterised by dwarfism, with sexual and mental retardation. It is caused by congenital deficiency of thyroid secretion. From the orthopaedic viewpoint the important features are retarded growth of the limb bones, kyphosis, and distortion of the joint surfaces. Early diagnosis is important because marked improvement follows treatment with thyroxine.

GLUCOCORTICOID EXCESS (Cushing’s syndrome)

This endocrine disorder is characterised by obesity, hypertrichosis, hypertension and, in women, amenorrhoea. It is induced by excessive secretion of adrenocortical hormones, caused either by a tumour of the adrenal cortex or by hyperplasia of the gland which may be secondary to a basophil adenoma of the pituitary. A similar condition may also be caused by prolonged administration of cortisone, prednisone, or related steroid drugs.

The orthopaedic significance of Cushing’s syndrome lies in the fact that it is accompanied by generalised rarefaction of the skeleton, with liability to pathological fracture of porotic bone (Table 6.1, p. 74).