The term brittle bone syndrome should not be confused with the considerably more common disease of osteoporosis which is frequently termed brittle bone disease. In osteogenesis imperfecta, which is usually transmitted as an autosomal dominant trait, the bones are excessively fragile.

Osteopetrosis is a rare genetic disease in which the bones become solidified and dense (Fig. 10.5), but brittle. There is inactivity of osteoclasts and absence of normal modelling resorption. Medullary spaces are minute (Fig. 10.6) and the epiphyseal ends of the bones are club-shaped. Because of the deficiency of marrow space, the liver and spleen take on blood-cell formation, but anaemia is common and defective white cells can lead to abnormal susceptibility to infection.

Achondroplasia is the most common type of genetic skeletal disorder and manifests itself as short-limbed individuals who historically became circus dwarfs. The essential defect is inability to form bone from cartilage at the epiphyses and base of the skull. This is due to a homozygous G1138A mutation at the 380 position in the fibroblast growth factor receptor 3 gene. This mutation, also termed G380R, is detectable prenatally to enable the diagnosis of the homozygous mutant type which is lethal in the newborn.

In this rare familial disorder, there is defective formation of the clavicles, delayed closure of fontanelles and sometimes retrusion of the maxilla. Partial or complete absence of clavicles allows the patient to bring the shoulders together in front of the chest (Fig. 10.7).

Cherubism causes multiple multilocular bone lesions in the mandible and maxilla that start in childhood, enlarge and then regress.

Cherubism is caused by one of several mutations in the SH3BP2 gene on chromosome 4p and is inherited as an autosomal dominant trait. The gene product is thought to be a signalling molecule but its exact function is unclear.

Though a dominant condition, there may be no family history because of variable expressivity and penetrance. As a result of weaker penetrance of the trait in females, the disease is approximately twice as common in males. Non-familial cases may also be new mutations. Usually, only isolated cases are encountered, but a family with no fewer than 20 affected members has been reported. The disorder may be seen almost worldwide, but appears to be rare in Japan.

The onset is typically between the ages of 6 months to 7 years, but rarely is delayed until late teenage or after puberty. Typically, symmetrical swellings are noticed at the age of 2 to 4 years in the region of the angles of the mandibles and, in severe cases, in the maxillae. The symmetrical mandibular swellings give the face an excessively chubby appearance (Fig. 10.9). The alveolar ridges are expanded and the mandibular swellings may sometimes be so gross lingually as to interfere with speech, swallowing or even breathing, but the rapidity of progress is variable. Teeth are frequently displaced and may be loosened.

Maxillary involvement is usually associated with widespread mandibular disease and is uncommon. Extensive maxillary lesions cause the eyes to appear to be turned heavenward; this together with the plumpness of the face, is the reason for these patients being likened to cherubs. The appearance of the eyes is due to such factors as the maxillary masses pushing the floors of the orbits and eyes upwards and also exposing the sclera below the pupils. Expansion of the maxillae may also cause stretching of the skin and some retraction of the lower lids. Rarely, destruction of the infra-orbital ridges weakens support for the lower lid. Maxillary involvement can also cause the palate to assume an inverted ‘V’ shape.

Despite lack of inflammation, there is frequently cervical lymphadenopathy, due to reactive hyperplasia and fibrosis. This is typically seen in the early stages and may completely subside by puberty.

Radiographic changes may be seen considerably earlier than clinical signs and are usually more extensive than the clinical swelling. The angles of the mandible are particularly involved, but the process extends towards the coronoid notch and sometimes also forwards along the body (Fig. 10.10). The lesions simulate multilocular cysts as a result of fine bony septa extending between the soft tissue masses. Panoramic radiographs help to determine the extent of the disease, but it is more clearly visualised by CT scanning.

Maxillary involvement is shown by diffuse rarefaction of the bone, but spread of lesions can cause opacity of the sinuses. A distinctive radiographic sign is exposure of the posterior part of the hard palate in lateral skull films, as a result of forward displacement of the teeth. Even after complete clinical resolution of the facial swelling, bone defects may persist radiographically. Growth is rapid for a few years, then slows down until puberty is reached. There is then slow regression until, by adulthood, normal facial contour is typically completely restored. However, radiolucent areas may persist longer. Severe cases may suffer permanent deformity, particularly if bony support for the eye has been destroyed.

Hypophosphatasia is an uncommon recessive genetic disorder. The early-onset type causes rickets-like skeletal disease with defective mineralisation. Defective cementogenesis results in premature loss of teeth and this is sometimes the only sign of the disease (see Fig. 2.30). Plasma alkaline phosphatase levels are low, but urinary phosphoethanolamine excretion is raised. Late-onset hypophosphatasia is sometimes a dominant trait and its main manifestation is fragility of the bones.

Bone changes are uncommon but, when severe, these diseases (see Ch. 25), particularly thalassaemia, can cause bony malformations of the maxillofacial region. In particular, expanded erythropoiesis causes thickening but osteoporosis of the bones of the skull. In sickle cell anaemia, infarcts in the jaws are painful. Symptomatically and radiographically, they can mimic osteomyelitis. Bone infarcts may appear relatively radiolucent at first, but become sclerotic and opaque areas in the skull or jaws are left by earlier infarcts.

In thalassaemia, the diploic spaces of the skull are enlarged due to marrow expansion and have a hair-on-end appearance radiographically and a thin cortex. The maxillae may also be expanded causing severe malocclusion. The zygomatic bones are pushed outwards and the nasal bridge depressed in severe cases.

This syndrome is an extremely rare autosomal dominant disease. Unlike sporadic hyperparathyroidism (see above), giant cell lesions do not develop.

Instead, cemento-osseous lesions form in the jaws. In addition to the jaw lesions, parathyroid adenomas or carcinomas, renal cysts, renal tumours and uterine tumours may be associated (see Ch. 31).

Overproduction of pituitary growth hormone, usually by an adenoma, before the epiphyses fuse, gives rise to gigantism with overgrowth of the whole skeleton. After fusion of the epiphyses, overproduction of growth hormone gives rise to acromegaly. The main features are continued growth at the mandibular condyle, causing gross prognathism, macroglossia, thickening of the facial soft tissues and overgrowth of the hands and feet (see Ch. 31).

Excessive amounts of fluorides in the drinking water, as in certain parts of Northern India, cause severe mottling of the teeth and also sclerosis of the skeleton. The intervertebral ligaments and muscle insertions calcify, causing stiffness (particularly of the back) and pain. Histologically, the bone changes are somewhat similar to those of Paget’s disease.

Vitamin D is essential for the absorption and metabolism of calcium and phosphorus. Deficiency during the period of bone development causes rickets with defective calcification and development of the skeleton, but rarely of the teeth (Ch. 30).

Defective calcium and phosphorus metabolism may also result from chronic renal disease (either hereditary or inflammatory) causing abnormal excretion of these minerals. Defective development of bone (renal rickets) can result.

The onset of rickets is usually in infancy. The main defects are broadening of the growing ends of bones and prominent costochondral junctions due to the epiphyseal defects (Fig. 10.13). The weakened bones bend readily. Typical changes in the skulls are wide fontanelles, bossing of the frontal and parietal eminences and thinning of the back of the skull. Radiographs show the wide, thick epiphyses and deformities (Fig. 10.13). There are usually normal serum calcium but low phosphorus levels, or either may be depressed. The alkaline phosphatase level is raised.

This term is given to familial hypophosphataemia. The skull sutures may be wide but the dental changes are more striking. The pulp chambers are abnormally large and calcification of dentine is defective. Pulpitis, often due to minimal caries, and apparently spontaneous dental abscesses are typical complications. Preventive dental care using fissure sealants and other means is therefore essential.

Scurvy, caused by vitamin C deficiency, leads to defective formation of collagen and osteoid matrix; such matrix as forms is well calcified. Infantile scurvy, with skeletal defects, is largely of historical interest in Britain but has been described, for instance, in an infant whose mother had eccentric ideas about diet. A case with gingival bleeding was described in 2000.

The amount of osteoid matrix formed is small but highly calcified so that the ends of the long bones are sharply defined radiologically. Weakness of the connective tissue and the haemorrhagic tendency (purpura) cause detachment of the periosteum by bleeding and bone pain. The haematoma becomes calcified as shown in the radiograph (Fig. 10.15).