By Dr. Colin Paterson
Extract of Dr Colin Paterson’s lecture at the NCHR’s Symposium, under the theme “Corruption and miscarriages of justice in child care cases” (Rättsröta och myndighetsmissbruk i barnavårdsärenden), which was held at Hotel Europa, Gothenburg, Sweden, June 5, 2004.
However, several bone disorders may also cause fractures to occur, apparently spontaneously or with normal handling, and unexplained fractures of whose presence the parents were unaware may be found on routine radiology. This presentation will outline these disorders and indicate the diagnostic clues that may be helpful. One frequent feature common in all of these disorders is the finding that superficial evidence of trauma is not commensurate with the number or types of fractures found on x-ray.The investigation of children in whom abuse is suspected includes a search for fractures. The finding of fractures, particularly fractures of the ribs and fractures at the ends of long bones (metaphyseal fractures), may be taken as evidence of non-accidental injury. This view is strengthened if the x-ray appearances suggest that the fractures are of different ages. If the parents or carers of the child deny causing injury, it may be assumed that they are lying or covering up for someone else.
The principal disorders known to cause unexplained fractures and difficulty in diagnosis are:
Temporary brittle bone disease
Bone disease of prematurity
Rickets due to vitamin D deficiency
Scurvy (vitamin C deficiency)
Copper deficiency and Menkes’ syndrome
This condition, often known as brittle bone disease, has been recognised for over a century. In recent years, it has become clear that most, but not all, cases are caused by genetic defects in the genes coding for collagen, the principal structural protein of bone and of other parts of the body. This protein is essential for the mechanical strength of bone. Although conventionally five distinct types of osteogenesis imperfecta are described, the reality is that there are many hundreds of different genetic defects. There is similarly great variation in the severity and clinical features of the condition. Some individuals are so severely affected that stillbirth or early neonatal death is inevitable. At the other extreme are people who have few or no fractures but yet are undoubtedly affected on the basis of family history or genetic investigation.
In many individuals osteogenesis imperfecta is inherited from one or other parent. The child of an affected parent has a one in two chance of being affected. ‘New mutations’ (new cases arising without any family history) are common.
Clinical features of osteogenesis imperfecta may include blue or grey colour of the sclerae (whites of the eyes), discoloration or fragility of the teeth, laxity of the joints, an increased tendency to bruising or pinpoint bruises known as petechiae. Deafness may occur in the teenage years or early adult life. Very few patients show all these features and some, undoubtedly affected, show none of the clinical features apart from fractures.
Fractures of all types occur in osteogenesis imperfecta. These include transverse, oblique, spiral and metaphyseal fractures of long bones, skull fractures, rib fractures and spinal fractures. Fractures may occur with little or no recognised force and fail to occur on other occasions when they might be expected. There is no consistent pattern to the fracturing; in many individuals there are long fracture-free periods.
X-ray appearances of the bone may be abnormal. However, in many patients, the bones appear normal at the time when the first few fractures are recognised. Measurements of bone mineral density often give normal results. Routine biochemical tests for, for example, blood calcium, phosphate and alkaline phosphatase levels are generally normal. However specialised laboratory investigations may help in diagnosis. One test involves taking a skin biopsy, culturing the fibroblast cells and examining the collagen produced. Another test involves examining the DNA obtained from a blood sample. Neither test shows abnormalities in all patients with osteogenesis imperfecta.
Temporary Brittle Bone Disease
Our research and that of others over the last nineteen years has provided evidence for the distinct variant to which we have given the name temporary brittle bone disease. This work remains very controversial and some have said that the disorder does not exist. However, we have increasingly good evidence that our work is accurate although the cause of the condition is not yet known.
In this disorder the fractures are limited to the first year of life and, to a large extent, the first six months of life. There may be very large numbers of fractures, particularly fractures of the ribs and metaphyseal fractures. Other clinical features in some cases include vomiting, which may be projectile, and anaemia. The family history may include joint laxity in one or other parent. The condition is common in children born pre-term and in twins. One risk factor appears to be diminished fetal movement in late pregnancy.
It is important to note that metaphyseal fractures (‘chip fractures’, ‘corner fractures’,
‘bucket-handle fractures’) are not specific for non-accidental injury but have a wide range of causes in addition to osteogenesis imperfecta and temporary brittle bone disease.
Four factors contribute to the view that temporary brittle bone disease is a real entity and not misdiagnosed non-accidental injury. First, the patients have many similarities both clinically and radiologically. Second, there is usually a substantial discrepancy between the radiological evidence of fractures and the clinical evidence of trauma. Third, the same syndrome occurs in situations in which non-accidental injury can be excluded with some confidence. Fourth, in over 70 patients returned to their parents there has been no subsequent evidence of physical abuse.
Bone Disease Of Prematurity
It has been known for many years that fractures, including spontaneous fractures, can occur in infants born before full-term. The fractures particularly include rib fractures and metaphyseal fractures but can occur at any site. Most published descriptions of the fractures in this condition report fractures limited to the first six months of life.
The cause of the disorder is not known. While it is often called rickets, there is no evidence that it is caused by lack of vitamin D. A number of tentative suggestions have been made including lack of the period of activity in late intra-uterine life which appears to be important for bone formation. It is not yet possible to delineate this disorder from temporary brittle bone disease.
Radiological signs sometimes include apparent diminution in bone density. Laboratory tests sometimes show a high blood level of the enzyme alkaline phosphatase.
Vitamin D is obtained partly from exposure to ultraviolet light and partly from a rather limited range of foodstuffs. In Europe vitamin D lack occurs particularly in certain groups of Asian immigrants in whom both cultural and dietary factors play a part. Mothers with vitamin D deficiency can give birth to infants with evidence of rickets at birth.
In most cases the radiological appearances help to make the diagnosis but not all patients show abnormality. Abnormal blood tests may include low levels of calcium or phosphate, high levels of alkaline phosphatase, increased levels of parathyroid hormone and low levels of the major form of vitamin D in blood, 25-hydroxyvitamin D. While fractures have long been recognised as a feature of rickets, x-rays may also show fracture-like appearances known as pseudo-fractures or Looser’s zones. These can be misinterpreted as fractures.
Vitamin C is essential for the formation of collagen and is obtained mainly from fruit and vegetables. In infancy vitamin C deficiency may cause fractures, periosteal reactions and metaphyseal abnormalities. Clinical features may include bruising and bleeding from the gums. Intracranial bleeding may occur. Laboratory investigations for vitamin C lack are not very satisfactory and the condition is probably under-diagnosed.
Copper Deficiency And Menkes’ Syndrome
Copper has an essential role in the formation of collagen. Lack of copper for any reason may cause a condition similar to temporary brittle bone disease. Recognised causes of copper deficiency include pre-term birth and prolonged periods of parenteral feeding but the cause is not always obvious. The investigation for this condition is unsatisfactory. Copper levels in blood may be misleading in not reflecting the copper stores in the body.
Menkes’ syndrome is a rare genetic disorder occurring in male children who suffer neurological deterioration and seldom survive beyond the age of three. It is an inborn defect in copper metabolism and, as with copper deficiency, spontaneous fractures may occur.
Colin R Paterson May 2004
Division of Medicine and Therapeutics
University of Dundee
Reports/gothenburg abstract 2004
- Paterson C R, McAllion S J. Osteogenesis impefecta in the differential diagnosis of child abuse. BMJ 1989; 299: 1451-4.
- Paterson C R. Osteogenesis imperfecta and other bone disorders in the differential diagnosis of unexplained fractures. J Roy Soc Med 1990; 83: 72-4.
- Paterson C R, Burns J, McAllion S J. Osteogenesis imperfecta: the distinction from child abuse and the recognition of a variant form. Am J Med Genet; 1993; 45: 187-92.
- Paterson C R, Monk E A. Long-term follow up of children thought to have had temporary brittle bone disease. Osteoporos Int 2000; 11 Supplement 4: S47-8.
- Paterson C R. Radiological features of the brittle bone diseases. J Diag Radiogr Imag2003; 5: 39-45.
- Miller M E. Temporary brittle bone disease: a true entity? Semin Perinatol 1999; 23: 174-82.
- Miller M E. The lesson of temporary brittle bone disease: all bones are not created equal. Bone 2003; 33: 466-74.