Temporary Brittle Bone Disease Research Articles

Overrepresentation of multiple birth pregnancies in young infants with four metabolic bone disorders: further evidence that fetal bone loading is a critical determinant of fetal and young infant bone strength

The frequency of multiple birth pregnancies, mostly twin pregnancies, was overrepresented in four different groups of young infants with fractures and bone abnormalities. This finding suggests that fetal bone loading through fetal movement is an important determinant of fetal bone formation and its resultant bone strength. It has been suggested that intrauterine confinement related to the multiple birth pregnancy (MBP) may lead to an increased risk for fragility fractures in young infants as a result of decreased fetal bone loading. To objectively test this idea, the frequency of MBPs was evaluated in five groups of young infants with bone disorders: (1) infants exposed to prolonged in utero exposure to magnesium, (2) infants with dietary copper deficiency, (3) infants with rickets from vitamin D deficiency, (4) infants with temporary brittle bone disease, and (5) infants with multiple unexplained fractures in which child abuse was the most likely diagnosis. Compared to a control group and controlled for preterm birth, there was a statistically greater frequency of MBPs in each group. The results of this study suggest the following: (a) The overrepresentation of MBPs (95% twins) in these five groups indicates that fetal bone loading is a critical determinant of fetal bone strength; (b) fetal and young infant bone strength is a multifactorial characteristic; and (c) infants from MBPs are at increased risk for fragility fractures during the first 12months of life, and thus may be mistakenly diagnosed as victims of child abuse.

Clinical and laboratory features of temporary brittle bone disease

Temporary brittle bone disease has been described since 1990. It is a syndrome characterised by multiple unexplained fractures in early childhood. There is growing evidence that it has natural causes and does not represent inflicted trauma. We report the clinical and laboratory features of 104 patients investigated personally between 1985 and 2000. These patients had in aggregate 976 fractures or fracture-like lesions. Our patients included disproportionate numbers of infants born preterm or as a result of multiple pregnancy. The fractures were mainly identified in the first 6 months of life and entirely within the first year of life. Most fractures were asymptomatic, particularly the many rib fractures and metaphyseal lesions. Few patients had evidence of bruising at presentation; none had clinical evidence of inflicted injury commensurate with the fractures found. In 22 patients the fractures were found in the course of investigation for unrelated symptoms. In several cases fractures took place while the children were in hospital. Unexplained bruising and sub-conjunctival haemorrhages also occurred in hospital, suggesting collagen defects. Hernias were recorded; in most these resolved spontaneously, again suggesting transient collagen defects. Among the unexplained symptoms of the patients was a history of vomiting, often projectile vomiting. Some patients had unusually blue or grey sclerae for the child's age. Many patients had abnormally large anterior fontanelles. Laboratory findings included anaemia, neutropenia and an exceptionally high serum alkaline phosphatase. Our findings reinforce the view that children with temporary brittle bone disease have a distinctive and identifiable syndrome which probably includes osteopathy of prematurity. These patients do not have osteogenesis imperfecta and are not the victims of non-accidental injury. While the causes of this syndrome remain uncertain, its distinctive features should now be more readily recognised.

Clinical features of temporary brittle bone disease

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

Temporary brittle bone disease: association with intracranial bleeding

We report 20 infants aged between 1 month and 6 months found to have subdural bleeding and also multiple unexplained fractures in a pattern similar to that described earlier as temporary brittle bone disease. Child abuse seemed unlikely as a cause of the fractures as in no case was there clinical evidence of injury commensurate with the fracturing, as some patients had fractures while in hospital and as metaphyseal lesions, when present, were often symmetrical in distribution. Abuse seemed unlikely to have been the cause of the subdural bleeding in several patients; three had clear histories of accidental injury and five had evidence that the initial bleeding was likely to have taken place at birth. Abuse also seemed unlikely as the cause of the syndrome; the nine patients who were returned to their parents had no subsequent allegations of abuse with a mean follow-up period of 15.8 years. The finding of hypermobile joints in the parents of eight of the children is an additional pointer to a natural cause for this condition. The cause of this combination of fractures and subdural bleeding is not yet clear but it is important to be aware that it can result from natural disease.

Temporary brittle bone disease: relationship between clinical findings and judicial outcome.

There is a wide differential diagnosis for the child with unexplained fractures including non-accidental injury, osteogenesis imperfecta and vitamin D deficiency rickets. Over the last 20 years we and others have described a self-limiting syndrome characterised by fractures in the first year of life. This has been given the provisional name temporary brittle bone disease. This work had proved controversial mostly because the fractures, including rib fractures and metaphyseal fractures, were those previously regarded as typical or even diagnostic of non-accidental injury. Some have asserted that the condition does not exist. Over the years 1985 to 2000 we investigated 87 such cases with fractures with a view to determining the future care of the children. In 85 of these the judiciary was involved. We examined the clinical and radiological findings in the 33 cases in which there was a judicial finding of abuse, the 24 cases in which the parents were exonerated and the 28 cases in which no formal judicial finding was made. The three groups of patients were similar in terms of demographics, age at fracturing and details of the fractures. The clinical similarities between the three groups of patients contrast with the very different results of the judicial process.

Joint laxity in the parents of children with temporary brittle bone disease

One controversial cause of unexplained fractures in young children is temporary brittle bone disease. Contributory factors for this disorder include the following: premature birth, twin pregnancy and diminished foetal movement. Heritable factors may also be important. Infants with findings consistent with temporary brittle bone disease were identified from clinical and medico-legal referrals. The routine evaluation of each family included examination of both parents where available for joint laxity using the nine-point Beighton scale. Of 81 children in whom both parents had been examined personally, 40 had at least one parent with a Beighton score of four or more, conventionally regarded as indicative of the hypermobility syndrome. We found no significant difference in laxity when we compared the whole group of mothers with the controls (P = 0.081). The fathers were significantly different from their control group (P = 0.013). When we compared the figures for the most flexible parent of each child, there were significant differences from control subjects both in the mothers and in the fathers (P = 0.042 and P = 0.0065, respectively). We draw attention to the likely autosomal dominant inheritance of this risk factor for temporary brittle bone disease as well as the potential value of assessing parental joint laxity in evaluating children with fractures.

Reply to Letter to the Editor: Unexplained Fractures: Child Abuse or Bone Disease: A Systematic Review

Reply to Letter to the Editor: Unexplained Fractures: Child Abuse or Bone Disease: A Systematic Review

Letter To the Editor: Unexplained Fractures: Child Abuse or Bone Disease: A Systematic Review

Letter To the Editor: Unexplained Fractures: Child Abuse or Bone Disease: A Systematic Review

Reply to Letter to the Editor: Unexplained Fractures: Child Abuse or Bone Disease: A Systematic Review

We thank Drs. Karst and van Rijn for bringing to our notice as well as that of the readership, issues regarding the study by Paterson et al. [2]. The fact that the existence of ‘temporary brittle bone disease’ as a variant of osteogenesis imperfecta has been challenged and in some ways shown to be nonscientific was known and of interest to us. We were, however, unaware (as an entire group of coauthors of our study [1]) of the court ruling from the United Kingdom related to the study Paterson et al. [2], and we welcome the clarification provided by Drs. Karst and van Rijn regarding the unscientific basis of ‘temporary brittle bone disease.’ Their point is even more relevant in light of the fact that the MOOSE group (Meta-analysis of Observational Studies in Epidemiology) state in their guidelines that because observational studies are vulnerable to bias confounding and chance, readers should consider explanations for the observations other than the conclusions of the authors [3]. However, had we known a priori about this issue, the study by Paterson et al. [2] still would have met our search criteria and our inclusion and exclusion criteria. As such, strict observation of systematic review technique would dictate that it be included. However, we would have made note of the controversy. Of note of the 914 cases we pooled in our study, the article by Paterson et al. [2] only contributed 39 cases (less than 5%). The omission of their article (based on the facts provided) would not have changed our main conclusion, which is that various bone disorders (primarily osteogenesis imperfecta, rather than temporary brittle bone disease) may be mistaken for child abuse. Again, we thank Drs. Karst and van Rijn again for bringing these facts to our attention.

Letter to the Editor: Unexplained Fractures: Child Abuse or Bone Disease: A Systematic Review

To the editor We read with interest the article by Pandya et al. [9]. Their review of the medical literature for bone diseases mimicking child abuse and neglect (CAN) is helpful with the very important interpretation of unexplained fractures. However, we do not understand why the study by Paterson et al., in which they introduced a variant form of osteogenesis imperfecta (OI) which they called ‘temporary brittle bone disease’ (TBBD) [11], was not excluded from the study. Paterson et al. suggested a temporary deficiency of an enzyme, involved in the posttransitional processing of collagen, as the underlying problem of TBBD in infants [11]. Others have suggested decreased fetal movement in utero might be the reason of temporary brittle bones [8]. No single clinical or laboratory study supports one of these theories. TBBD is not clinically validated nor generally accepted by expert professionals [4, 5, 7]. The Supreme Court in the United Kingdom concluded in a 2001 case that Paterson’s TBBD theory had no scientific basis and the investigation was subjective, unreliable, nonscientific, and nonproven [1]. In 2004 the General Medical Council removed Paterson from their register of practicing physicians in the United Kingdom because “he ignored crucial evidence to advance his own controversial theories on bone disease” [3]. Paterson recently published five more cases on infants with multiple rib fractures [10], which he presented as evidence for the existence of TBBD. Letters to the editor showed once again the complete lack of validation for the entity [6, 12]. Crucial additional information in these cases, such as data from brain imaging, eye examinations, or a complete skeletal survey, were not provided [10]. There was no review of the radiologic images by a pediatric radiologist [10]. In four cases there were no data on examination for skin injury [10]. Being unaware of the lack of scientific basis for the existence of TBBD is dangerous, as the important evaluation of fractures in young children might lead to incorrect conclusions, possibly resulting in ongoing risk for the child or other children. In our opinion TBBD should be considered a theory without any scientific basis. This background information should have been provided in the otherwise instructive review by Pandya et al. [9].

Long-term follow-up of children thought to have temporary brittle bone disease

correspondence: colin r Paterson Temple Oxgates, Longforgan, Dundee DD2 5Hs, scotland Tel +44 1382 360240 email c.s.paterson@btinternet.com Background: In addition to nonaccidental injury, a variety of bone disorders may underlie the finding of unexplained fractures in young children. One controversial postulated cause is temporary brittle bone disease, first described in 1990. Methods: Eighty-five patients with fractures showing clinical and radiological features of temporary brittle bone disease were the subject of judicial hearings to determine whether it was appropriate for them to return home. Sixty-three patients did, and follow-up information was available for 61 of these. The mean follow-up period was 6.9 years (range 1–17, median 6). Results: We found that none of the children had sustained any further injuries that were thought to represent nonaccidental injury; no child was re-removed from home. Three children had fractures. In each case there was general agreement that the fractures were accidental. Had the original fractures in these children been the result of nonaccidental injury, it would have been severe and repeated; the average number of fractures was 9.1. Conclusion: The fact that no subsequent suspicious injuries took place after return home is consistent with the view that the fractures were unlikely to have been caused by nonaccidental injury, and that temporary brittle bone disease is a distinctive and identifiable disorder.

Nonaccidental Trauma in Children: Editorial Comment

Nonaccidental Trauma in Children: Editorial Comment

Unexplained Fractures: Child Abuse or Bone Disease? A Systematic Review

BackgroundChild abuse and neglect (CAN) is a serious problem that has major implications for the welfare of the child involved. Unexplained fractures are of particular concern to the orthopaedic surgeon, who must often consider alternative diagnoses to CAN.Questions/purposesWe therefore (1) determined which bone diseases most commonly mimic CAN; (2) what types of osteogenesis imperfecta (OI) are most commonly confused with CAN and why; and (3) what specific findings in OI and bone disease render a mistaken diagnosis of CAN more likely.MethodsA systematic review of the literature was performed. We identified studies that compared cases of CAN with cases in which patients had bone disease that resulted in an unexplained fracture. We also included studies in which patients with fractures resulting from underlying bony pathology were misclassified as CAN and were subsequently reclassified as bone disease as a result of further investigation. Our search netted only five studies that directly compared and contrasted CAN with metabolic or genetic bone disease in the same study.ResultsThe published literature suggests OI is most frequently confused with CAN, although metaphyseal dysplasia, disorders of phosphate metabolism, and temporary brittle bone disease are also documented in the literature identified by our search. Difficulty in differentiating these bony diseases from CAN stems from ambiguity in the history and physical examination at the time of presentation.ConclusionsBone disease is a diagnosis of exclusion in the differential diagnosis of CAN.

Does temporary brittle bone disease exist? Not by the evidence offered

Does temporary brittle bone disease exist? Not by the evidence offered

Cases do not support temporary brittle bone disease

Cases do not support temporary brittle bone disease

Temporary brittle bone disease: fractures in medical care

Temporary brittle bone disease is the name given to a syndrome first reported in 1990, in which fractures occur in infants in the first year of life. The fractures include rib fractures and metaphyseal fractures which are mostly asymptomatic. The radiological features of this disorder mimic those often ascribed to typical non-accidental injury. The subject has been controversial, some authors suggesting that the disorder does not exist. This study reports five infants with typical features of temporary brittle bone disease in whom all or most of the fractures took place while in hospital. A non-accidental cause can be eliminated with some confidence, and these cases provide evidence in support of the existence of temporary brittle bone disease.

The death of temporary brittle bone disease is premature

The death of temporary brittle bone disease is premature

Classic metaphyseal lesions follow uncomplicated caesarean section NOT brittle bone disease

Sir, We appreciate the interest shown in our article by Dr. Miller. We do not, however, agree with his suggestion that the metaphyseal fractures identified in the three infants born at our institution over a 22-year period may have been due to a lower newborn bone strength caused by fetal immobilization as a result of their breech presentation or maternal diabetes. Although none of these infants had bone densitometry performed, the plain radiographs obtained showed no evidence of osteopenia. A workload audit is performed annually in our hospital. A review of the past 22 years has revealed a total of 2,313 multiple pregnancies, 2,622 infants who had a breech presentation, 1,814 of whom were delivered by caesarean section and 664 infants born to mothers who had insulindependant diabetes mellitus. Over the past 15 years there have been a further 1,199 infants born to mothers with gestational diabetes. If this large group of infants, as Dr. Miller proposes, were likely to have decreased bone strength and increased susceptibility to fractures, we would expect to have identified many more such metaphyseal injuries. In addition, we are not aware of any reports of an increased incidence of metaphyseal fractures in other institutions caring for similar large patient groups. Finally, we would like to draw Dr. Miller’s attention to the article “Critical review of ‘temporary brittle bone disease’” by Kenneth Mendelson in this journal in 2005, which, following detailed literature analysis, concludes that Miller and Hangartner [1] failed to demonstrate a relationship between fracture patterns and intrauterine confinement or decreased bone density [2].

Another perspective on the cause of metaphyseal fractures

Sir, I read with interest the article by O’Connell and Donoghue [1] that describes three newborn infants with classic metaphyseal fractures (CMLs) following cesarean delivery. All of the CMLs were diagnosed radiographically or by clinical features on day 2 of life. Two of the infants were in the breech presentation, and in the third case the mother had poorly controlled gestational diabetes. While the authors attribute these fractures to twisting and pulling of the extremities during delivery, and possibly to large size (all three infants weighed >3.45 kg), there are many such infants born in a similar fashion who never show any evidence of bone fractures. The critical issue is whether these three infants may be predisposed to having lower newborn bone strength, and I would suggest that fetal immobilization is likely the common thread to understanding such a predisposition in these three infants. Application of the Utah paradigm to the in utero development of fetal bone strength would suggest that bone loading through fetal movement is critical to the realization of normal bone strength at the time of birth [2]. Situations that diminish fetal movement will decrease bone strength and include the following: cephalopelvic disproportion, malpresentation (including breech presentation), twin pregnancy, prematurity, oligohydramnios, large maternal fibroids, and maternal use of medications that can cause decreased fetal movement [3, 4]. Since two of the three infants were in the breech presentation, it is likely that they may have been confined and moved less than normal while in utero. It is known that infants of diabetic mothers have a lower bone mineral content at birth compared to controls as a result of increased bone resorption [5, 6]. It is also known that infants of diabetic mothers have decreased cyclic movements compared to normal controls, and this relative fetal immobilization would explain the osteoclast-mediated osteopenia in infants of diabetic mothers [7]. Case reports such as those in the article by O’Connell and Donoghue support the existence of a transient brittle bone state from fetal immobilization that can lead to the same types of fractures as seen in child abuse [1, 8]. CMLs associated with physical therapy in the treatment of clubfeet have also been described in this journal, and it has also been noted that some of these cases were also associated with fetal immobilization [9, 10]. The idea of decreased fetal bone loading leading to decreased bone strength has a scientific foundation based on experimental observations and is in accord with contemporary thinking of bone physiology [2, 8, 11, 12]. The authors imply that CMLs are specific for abuse unless there is a prior history of accidental injury. I disagree with this position. In the cases they present, what would have happened if the swelling and leg abnormalities were not noted until after the newborn infants had been discharged from the hospital and were in the care of the parents? Child abuse would have been alleged against the parents. There is a differential diagnosis for metaphyseal fractures that includes copper deficiency, Menkes disease, scurvy, hyperparathyroidism, osteogenesis imperfecta, temporary brittle bone disease from fetal immobilization, physical therapy for clubfoot, breech presentation with/ without external version, the bone disease of prematurity, fetal exposure to magnesium, and child abuse [1, 13, 14]. Pediatr Radiol (2008) 38:598–599 DOI 10.1007/s00247-008-0758-4

Evaluating Infants and Young Children With Multiple Fractures

Infants and toddlers with multiple unexplained fractures are often victims of inflicted injury. However, several medical conditions can also cause multiple fractures in children in this age group. In this report, the differential diagnosis of multiple fractures is presented, and diagnostic testing available to the clinician is discussed. The hypothetical entity "temporary brittle-bone disease" is examined also. Although frequently offered in court cases as a cause of multiple infant fractures, there is no evidence that this condition actually exists.