Judge Relies On Controversial Medical Argument

A judge attacks my ‘one-sided’ child protection stories – but it cuts both ways

The judgment that Mr Justice Bellamy has published makes for illuminating reading, and not just for its attack on me, says Christopher Booker.

In March, the number of applications by social workers to take children into care set a new record: 882 in a single month. Over the past year, my reports on how our highly secretive “child protection” system seems, too often, to collude in seizing children without proper justification have provoked considerable irritation in a number of judges – and last week the judiciary hit back. Mr Justice Bellamy, presiding over a case to which I have referred several times, took the unusual course of publishing a judgment in which he was highly critical of me for my “unbalanced” and “inaccurate” reporting. Then the head of the family courts, Lord Justice Wall, in his ruling on another case, swiftly endorsed Bellamy’s attack on me (despite his own earlier criticisms of the “shocking” determination of some social workers to place children in “an unsatisfactory care system”).

I am not displeased that Bellamy has published his judgment, because the main part of it provides a rare opportunity to see how a judge may rely on a particular medical argument which has become increasingly controversial. But first I must deal with his criticism of my reporting. In the many hundreds of words I have written about this case, on five separate occasions, he singled out only two points as inaccurate. On one of these he was right: I was misinformed that a particular medical witness had appeared in another of Bellamy’s cases.

The next day, however, the judge had to add a supplementary judgment, correcting some of what he had said. It emerged that he had made several factual errors in his references to me. These included misquoting what I had written, through reliance on a website (which he misspelt), and claiming that my articles had appeared in The Daily Telegraph.

Bellamy went on, however, to use my two errors as his text for a general homily on how inexcusable it is to give a tendentious account of family cases based on a one-sided picture given by aggrieved parents. This might sound damning to anyone unfamiliar with the whole secretive system, but it takes no account of the extraordinary obstacles placed in the way of any journalist wishing to report fairly on them.

On more than one occasion when I approached a local authority to check on the facts of what seemed a very disturbing case, the only response was to seek a gagging order prohibiting me from mentioning the case at all. When I accurately reported on one case so embarrassing to the council concerned that it eventually dropped its bid to seize a child, the judge ruled that any future reference to the case outside the court could lead to summary imprisonment.

So the only recourse left to those trying to establish the facts of such cases is rigorously to test what can be learned from the few people willing to speak, and to come to as informed and judicious a view as possible.

Something else came to light in Bellamy’s judgment, however, that is far more important than his criticism of me. The case before him concerned a couple who last year became so concerned that their six-week old baby had developed a “floppy arm” that in the middle of the night they took it to hospital to be examined. X-rays showed the child had suffered a “non-displaced” fracture of the humerus. The police were summoned to arrest the parents, who were led off in handcuffs and held for hours in police cells. Coventry social workers took the child into care and the police charged the father with physically abusing his son.

Now the judge has delivered his fact-finding judgment, on the basis of which he will decide the child’s future in September, we can see, for the first time, that its injuries included not only the fractured arm but also six “metaphyseal fractures” and several marks or bruises. (“Metaphyseal” refers to the metaphysis, the part of a long bone near where it meets a joint, the part that grows in childhood.) All of this sounded like a very grave set of injuries, which might point to serious physical abuse.

The court heard that in every other respect the couple seemed to be devoted, conscientious parents, anxious only to do the right thing by their child. But what clearly weighed most heavily with the judge were those “metaphyseal fractures”. He heard evidence from no fewer than four medical experts that metaphyseal fractures are a virtually certain sign of “non-accidental injury” (a phrase used 20 times in his judgment), implying intentional physical harm.

Finding on this basis that the child had definitely been abused, Bellamy then saw it as his duty to identify the “perpetrator”. Based on the timing of the events that led to the parents rushing their child to hospital, he concluded that the main injury must have been inflicted in a brief interval when the father was out of the room, and the person responsible must have been the mother. The police, he argued, had been wrong to charge the father (a charge still awaiting trial). The judge was thus, in effect, accusing the mother of a crime.

The problem with regarding metaphyseal injuries as an indicator of abuse is that in recent years ever more medical experts have strongly questioned the idea. Their studies show that metaphyseal fractures may occur in babies with soft, still-forming bones, with minimal trauma. They even question whether such injuries can be properly described as fractures at all. The real explanation, they believe, lies in a metabolic bone disease, a contributory factor to which may be a deficiency in Vitamin D (of the type which evidence showed the mother in our present case to have). Only this month a leading American expert, Dr Marvin Miller, published a major new study suggesting that “the cause of multiple unexplained fractures in some infants” might be “metabolic bone disease, not child abuse”.

Also something of an expert on this subject is Dr James Le Fanu of this newspaper, who in 2005 published a paper in the Journal of the Royal Society of Medicine entitled “The wrongful diagnosis of child abuse: a master theory”. In another paper, “The misdiagnosis of metaphyseal fractures: a potent cause of wrongful accusations of child abuse”, he described how the theory of metaphyseal fractures as characteristic of child abuse, first advanced by Dr Paul Kleinman in the US in 1986, was taken up by a small group of radiologists in Britain who became much in demand in our courts as expert witnesses. In 2005, under the headline “Happy, loving parents? They must be child abusers”, Dr Le Fanu explained in these pages how reliance on this diagnosis in the criminal courts was already strongly contested, to the point where it became discredited. But in the family courts, he wrote – citing a case remarkably similar to the one before Mr Justice Bellamy today – the theory was unchallenged.

It is certainly noticeable from Bellamy’s account of the evidence that it was all strictly according to Kleinman’s theory. The four expert witnesses he heard all came across as committed advocates of the Kleinman thesis, in arguing that metaphyseal fractures are an indicator of child abuse. For whatever reason, not one expert was called who was prepared to challenge that view. Bellamy himself said that these injuries are often regarded as “pathognomonic of abuse”, meaning they can have no other cause – seemingly unaware that there is a growing body of scientific opinion to suggest that this may not be their cause at all.

The lawyers for the mother, who has effectively been accused by the learned judge of a criminal act, are said to be considering an appeal against Bellamy’s ruling. If so, one hopes they will take the opportunity to call expert witnesses ready to challenge this still prevailing orthodoxy, on the basis of which scores of children have been removed from loving and conscientious parents – so that the bench on that occasion can at least be given a rather less “one-sided” view.

By:

By Christopher Booker 7:00PM BST 14 May 2011

Source:

http://www.telegraph.co.uk/comment/columnists/christopherbooker/8513956/A-judge-attacks-my-one-sided-child-protection-stories-but-it-cuts-both-ways.html

Fractures believed to be child abuse may be metabolic bone disease

Pediatric Academic Societies’ Annual Meeting 2011

New data suggest that metabolic bone disease, not child abuse, may be the cause of multiple unexplained fractures in some infants.

“Classic metaphyseal lesions, posterior rib fractures and fractures in different stages of healing are thought to be pathognomonic for child abuse,” researchers wrote. “However, we believe these findings can also be seen in metabolic bone disease of infancy.”

To investigate this theory, a radiologist reviewed X-rays of 63 infants with multiple unexplained fractures for features of metabolic bone disease; their fractures were originally considered child abuse. The researchers also searched the patients’ medical charts for the following factors that predispose children to metabolic bone disease: vitamin D deficiency in pregnancy and infancy; decreased fetal bone loading, including intrauterine confinement, malpresentation and maternal use of drugs that cause fetal immobilization; gestational diabetes; and use of drugs that decrease calcium absorption, such as acid-lowering drugs.

Results revealed that, on average, infants presented with fractures at 12.5 weeks of age, with each infant experiencing an average of nine fractures. The researchers identified 171 classical metaphyseal lesions in 42 infants and multiple rib fractures (≥4) in 29 infants. Although the researchers suspected epiphyseal separations in 6% of classical metaphyseal lesions, the majority were clinically silent and healed without callus or periosteal reaction.

X-ray images revealed that features of metabolic bone disease were present in all infants, the researchers said. Seventy-three percent of the pregnancies had evidence of fetal immobilization. Data showed that 52% of the infants tested and 87% of their mothers had abnormally low 25-hydroxyvitamin D levels. Thirteen percent of mothers also had gestational diabetes. The researchers noted that acid-lowering drugs were used by 14% of mothers during pregnancy and in 18% of the infants. Decreased fetal bone loading also occurred during 43% of pregnancies.

These results suggest that physicians should consider metabolic bone disease when encountering infants with multiple fractures, according to the researchers.

“Careful review of the X-rays with attention to the predisposing factors that can impair fetal and infant bone mineralization is critical to avoid an erroneous diagnosis of child abuse,” they wrote. “We do not believe that most [classical metaphyseal lesions] are fractures, but rather are regions of non-mineralized osteoid in healing [metabolic bone disease in infancy].”

For more information:

• Miller ME. Poster 1403.31. Poster session: Endocrinology & diabetes. Presented at: Pediatric Academic Societies 2011; April 30-May 3, 2011; Denver.

Source:

http://www.endocrinetoday.com/view.aspx?rid=83202

Osteogenesis imperfecta the distinction from child abuse and the recognition of a variant form

Unexplained fractures are characteristic of both osteogenesis imperfecta (OI) and non-accidental injury (NAI) but in most cases the diagnosis is straightforward. However, in a few OI patients an initial diagnosis of NAI is made. Factors contributing to such difficulties include failure to recognise that OI can occur without a family history, without blue sclerae, without osteopenia, without an excess of Wormian bones, or with metaphyseal fractures. In addition we report on 39 patients with an unusual history in that fractures only occurred in the first year of life. Rib fractures, metaphyseal abnormalities and periosteal reactions were common. The initial diagnosis was usually OI if the fractures occurred in hospital, but NAI if they appeared to have been sustained at home. Additional findings such as anaemia, vomiting, hepatomegaly, and apnoeic attacks were often found in these patients. The disorder has some similarities to the syndrome of infantile copper deficiency. Like the latter it is particularly common in preterm infants and in twins. Therefore, we are attempting to examine the incidence of significant hypocupraemia in unselected preterm infants. We suggest that the likely cause of this “temporary brittle bone disease” is a temporary deficiency of an enzyme, perhaps a metalloenzyme, involved in the post-translational processing of collagen.

C R Paterson; J Burns; S J McAllion

Title:  American journal of medical genetics     Volume:  45     ISSN:  0148-7299     ISO Abbreviation:  Am. J. Med. Genet.     Publication Date:  1993 Jan

Department of Biochemical Medicine, University of Dundee, Scotland

http://www.biomedsearch.com/nih/Osteogenesis-imperfecta-distinction-from-child/8456801.html

Radiological Signs In Rickets And Their Differential Diagnosis

Abstract

1.	Radiological changes in the bones in infantile, late and adult types of rickets and their differential diagnosis have been described and illustrated by cases seen at Nagpur in the Medical College Hospital during the last two years.
2.	Radiological changes are a replica of the histological changes in the bones and they occur both in the shaft and at the cartilage shaft junction.
3.	Changes at the growing metaphysis are its broadening fuzziness and cupping; fading out of the epiphyseal plate and in severe cases non-calcification of the metaphysis. These are present only if growth is occurring at the bone end.
4.	Changes in the shaft are rarefaction, reticulation of the spongiosa, deformities, fractures and pseudofractures.
5.	Physiological cupping of lower ends of radius and ulna, growth lines, lead, phosphorus and bismuth lines, congenital syphilis, scurvy, osteogenesis imperfecta, hyperparathyroidism, postmenopausal osteoporosis and renal osteodystrophy have been discussed in differential diagnosis.
6.	A case of infantile rickets with multiple fractures and pseudofractures and another of renal rickets are recorded.

From the Department of Pediatrics, Medical College, Nagpur.

Source:

http://www.springerlink.com/content/4580p1k11124w622/

The Bone Disease of Preterm Birth: A Biomechanical Perspective

MILLER, MARVIN E.

Author Information

Department of Pediatrics, Wright State University School of Medicine, Dayton, OH 45404, U.S.A.

Received July 17, 2001; accepted August 22, 2002.

Correspondence: Marvin Miller, M.D., Children’s Medical Center, Department of Medical Genetics, 1 Children’s Plaza, Dayton, OH 45404, U.S.A.; e-mail: srmmem@aol.com

Supported, in part, by the Children’s Medical Center Research Foundation, Dayton, OH, U.S.A.

Abstract

The bone disease of preterm birth has traditionally been explained by a decrease in bone formation from insufficient availability of calcium and phosphorus. However, there is emerging evidence that there is increased bone resorption in the bone disease of preterm birth, an observation that indicates some other explanation for this condition. The biomechanical model of postnatal bone formation states that, through a regulatory feedback system in the bone called the mechanostat, bone is able to respond to increased bone loading by increasing bone strength and to decreased bone loading by decreasing bone strength. It is suggested that this increased bone resorption in the markedly preterm infant compared with the term infant is secondary to decreased bone loading. Application of this model to the fetus and preterm infant suggests that intrauterine bone loading of the fetus from movement and kicking against the uterus is critical for normal fetal bone formation. The associated muscle growth from this activity also contributes to bone loading. The markedly preterm infant is deprived of much of this critical time period of intrauterine bone accretion, and bone formation occurs in the less favorable extrauterine environment, where there is significantly less bone loading.

Abbreviation: VLBW, very low birth weight

Infants who are born at 24, 25, and 26 wk of gestation now have a 50%, 70%, and 80% likelihood for survival, respectively ⁽¹⁾. This increasing survival rate of VLBW (VLBW = birth weight <1500 g), preterm infants over the past 30 y has created new medical diseases in these fragile infants that did not previously exist. One such disease is the bone disease of preterm birth in which approximately 10% of VLBW, preterm infants incur fractures within the first several months of life. The mean age of diagnosis of fractures in one series of preterm infants with fractures was 76 d, and the types of fractures included long bone, rib, and metaphyseal fractures ⁽²⁾. The specific cause of the bone disease of preterm birth must explain the observation that the rate of bone accretion for a fetus in an intrauterine environment is greater than that for a preterm infant in an extrauterine environment. Thus, the bone density of a full-term infant who is born at 40 wk of gestation is greater than that of a 12-wk-old preterm infant who is born at 28 wk of gestation ⁽³⁾.

It has been assumed that this difference in bone accretion rates in the intrauterine versus the extrauterine environment is from the difference in availability of calcium and phosphorus, the essential minerals needed for bone formation ⁽⁴⁾. There is an exponential increase in bone formation during the last trimester during which approximately 80% of fetal bone is produced as the whole-body calcium increases from approximately 5 g at 24 wk of gestation to approximately 30 g at term, 40 wk of gestation ⁽⁵⁾. The peak accretion rate for bone occurs at approximately 35 wk of gestation, when the calcium accretion rate is approximately 150 mg/kg/d and the phosphorus accretion rate is approximately 75 mg/kg/d. It is interesting that there is a dramatic decrease in calcium accretion in the last 5 wk of pregnancy ⁽⁶⁾. For adequately meeting this large demand for calcium and phosphorus during this rapid period of bone formation during the last trimester, there is active transplacental transport of calcium and phosphorus from the mother to the fetus ⁽⁷⁾. It has been assumed that for normal extrauterine bone formation in a VLBW, preterm infant, similar daily requirements of calcium and phosphorus are needed. However, in the extrauterine environment, it is difficult to achieve this level of calcium and phosphorus delivery in the VLBW, preterm infant with enteral formulas or hyperalimentation ⁽⁸⁾. The cause of the bone disease in preterm birth has been ascribed to this particular issue of mineral substrate availability. Contributing factors to the bone disease of preterm birth include chronic illness, prolonged hyperalimentation, bronchopulmonary dysplasia, and the use of hypercalciuric drugs such as furosemide for treatment of bronchopulmonary dysplasia and methylxanthines for treatment of apnea and bradycardia, both of which increase calcium losses ⁽⁸⁾.

Back to Top | Article Outline

INCREASED BONE RESORPTION IN THE BONE DISEASE OF PRETERM BIRTH

Although the notion that decreased bone formation from diminished availability of calcium and phosphorus has traditionally been thought to be the primary cause of the bone disease of preterm birth, there are two observations that suggest otherwise and provide evidence of increased bone resorption in the bone disease of preterm birth. First, two separate groups have found urinary bone resorption markers in much greater concentration in preterm infants compared with term infants ^{(9, 10)}. Markers of bone resorption included collagen turnover compounds (hydroxyproline, type 1 collagen telopeptide), calcium, and phosphate. Beyers et al. ⁽⁹⁾ noted that preterm infants at expected full-term age had significantly greater urine excretion of calcium (2.9×), phosphate (4.3×), and hydroxyproline (3.7×) compared with normal term infants. Serum alkaline phosphatase was twice as great (411 U/L versus 206 U/L) in preterm infants at expected full-term age compared with the normal term infants. Moreover, radiologic evaluation showed increased endosteal resorption in the preterm infants. Mora et al. ⁽¹⁰⁾ found that preterm infants (average gestational age of 33 wk) had significantly higher blood levels of type 1 collagen telopeptide than term infants when both groups were studied at 4 wk of age. Using osteocalcin and procollagen type 1 carboxyterminal propeptide as indices of bone formation, these investigators found lower levels of bone formation in the preterm infants than the term infants. Others have also found an increased renal excretion of calcium and phosphorus in the preterm infant compared with the term infant ⁽¹¹⁾.

Second, VLBW, preterm infants who are fed formula preparations with higher calcium and phosphorus content usually do not have an increased bone density ⁽¹²⁾. If the bone disease of preterm birth were caused solely by calcium and phosphorus deficiency, then these two observations would not be expected. The totality of evidence points to some other factor or additional factor than just calcium and phosphorus availability as the basis for the bone disease of preterm birth.

What specific factor could explain this difference in bone resorption in the preterm versus term infant? In the past, a biochemical perspective has been taken in trying to understand human bone disease as shown in Figure 1A. This approach has failed to provide adequately an understanding of the bone disease of preterm birth, because it ignores biomechanical factors. If a biomechanical perspective is taken, then the bone disease of preterm birth is easily understood as shown in Figure 1B. The answer to this conundrum is in the difference in bone loading of the skeletal system in the preterm infant compared with the term infant.

BIOMECHANICAL MODEL OF BONE FORMATION

Frost ⁽¹³⁾ proposed the mechanostat/mechanical loading model of postnatal bone formation, which states that the primary factor in the development of bone strength is the load (force) placed on the bone. The load causes a strain on the bone, which is transmitted to the mechanostat as an input signal. The mechanostat is a sensor within the bone that can evaluate the input of strain from a given load placed on the bone and then direct an appropriate output to the effector cells, osteoblasts and osteoclasts. Strain is the proportional change in length caused by a load and can be from compression, tension, or shearing loads. If a bone specimen is stretched by 1% of its length, then it is said to be undergoing a strain of 1%, or 10,000 microstrain. If a bone specimen is compressed by 0.1% of its original length so that it is now 99.9% of its original length, then it would be undergoing a strain of 1000 microstrain. Loads always cause strains even when they are small.

The mechanostat thus is the brain of the bone and functions as a feedback or regulatory system to keep bone strength commensurate with the loads placed on the bone. The mechanostat processes the strain input and compares it with preset, threshold levels of strain for increasing bone strength or decreasing bone strength. The mechanostat is then able to generate an appropriate output signal to effector cells to bring about the needed change in bone strength to align the strain within given limits. Effector cells are osteoblasts that produce bone and osteoclasts that resorb bone. If significantly increased loads that exceed the threshold for increasing bone strength are placed on a bone, then the mechanostat signals the effector cells to increase bone strength. If significantly decreased loads that exceed the threshold for decreasing bone strength are placed on a bone, then the mechanostat signals the effector cells to decrease bone strength. If the strain does not exceed either of these thresholds, then the effector cells operate at a status quo, or baseline, level of activity.

Osteoblast and osteoclast activity can change bone strength through either altering bone density or altering bone architecture through two distinctly different processes of bone physiology: bone modeling and bone remodeling. Both modeling and remodeling are processes that respond to bone loading through the mechanostat.

Modeling is the process by which bone is sculpted to the most advantageous geometry, both for bone strength and for appropriate attachment of muscles and tendons. As bone grows, some bone must be added to certain surfaces and some bone must be removed from other surfaces. The bone achieves this result through formation drifts and resorption drifts. Formation drifts influence osteoblasts to build up some bone surfaces, whereas resorption drifts influence osteoclasts to remove bone from some bone surfaces. Modeling results in changes of bone size or shape or of both and thus is a prominent process in bone development during fetal life and in childhood. In bone modeling, osteoblasts and osteoclasts function independent of each other, and each cell type responds to a certain preset modeling threshold within the mechanostat. Modeling almost always increases bone strength either by increasing bone mass or by favorably altering bone architecture.

Remodeling is the process whereby fatigued bone is efficiently removed and then replaced by new, intact bone by the sequential activity of osteoclasts to resorb the fatigued bone followed by osteoblasts to produce new bone. In bone remodeling, osteoblasts and osteoclasts act cooperatively in a coupled manner in a unit called a basic multicellular unit. This coordinated activity is also realized when a certain preset threshold of strain is sensed by the mechanostat.

There are two types of bone loading. The first is associated with the direct contact or impact of bone against another object, such as the increased load that the leg bones realize during running or from the resistance that a bone might experience such as the extremities realize in swimming. The second is associated with the active and passive load that the bone senses from the muscles attached to it. The muscles that attach to a bone exert a small but continuing load on the bone even when the muscle is not actively moving the bone. The loading of the skeletal system from attached muscles is critical in maintaining bone density. Weightlifters have greater bone density than nonweightlifters ⁽¹⁴⁾. Children with chronic, neuromuscular diseases associated with muscle paralysis and muscle weakness have osteopenia and an increased risk for fracture ⁽¹⁵⁾.

Frost called this model the Utah paradigm, which is an ever-evolving paradigm that includes nutrient, hormonal, cellular, biochemical, and biomechanical factors ⁽¹⁶⁾. The centerpiece of the Utah paradigm is the notion that bone strives to be a mechanically competent tissue through the operation of the mechanostat to sense strain from the loads placed on the bone and appropriately respond to these strains by increasing or decreasing bone strength. Others have also underscored the importance of mechanical considerations in skeletal health and disease ^(17-19).

According to the Utah paradigm, bones are formed in two distinct steps ⁽¹⁶⁾. The first step is the embryogenesis of the skeletal system. Between 5 and 12 wk of gestation, multiple, specific genes direct condensations of mesenchyme to specific anatomic locations that are destined to become the precursor tissues of bone that will eventually chondrify and ossify ⁽²⁰⁾. In a similar time period during the first trimester, other specific genes direct ventral and dorsal condensations of somitic mesoderm to become precursor tissues of skeletal muscle, and these will eventually attach to their appropriate bones. By 16 wk of gestation, the anatomy, anatomical relationships, and biologic machinery for adaptation of bones are in place. This state of bone is called the baseline conditions.

The second step of bone formation, beginning during the midportion of the second trimester, is the state of responsiveness of the skeletal system to genetically defined bone proteins and humoral mediators, nutrient considerations, and mechanical factors. Long bones grow both in length and in diameter. Linear bone growth of the long bones is determined primarily by specific genes through enchondral ossification. However, long bones assume their final, normal geometry, through the process of modeling. Modeling uses osteoblasts to form bone and osteoclasts to remove bone. Diametrical bone growth of long bones occurs through modeling in which osteoclasts remove bone from the endosteum and osteoblasts form bone along the periosteum. Flat bones, such as the scapula, pelvis, and skull, grow through intramembranous bone formation. Modeling that is responsive to bone loading occurs in enchondral and intramembranous bone formation in both the prenatal and postnatal periods. During the second and third trimesters, bone modeling also responds to increasing muscle forces. As the skeletal system of an individual ages, the adaptations for any given bone, which include growth, modeling, and remodeling, are added to the baseline conditions of the bone.

At the same time that bone modeling begins, fetal movement commences at approximately the 16th wk of gestation. Bone modeling is strongly influenced by bone loading, and bone loading during fetal life is determined primarily by fetal movement. Fetal movement leads to bone loading in three ways:1) the loading associated with the impact of the fetus, especially the extremities, against the uterus;2) the loading associated with the resistance against movement in the amniotic fluid; and 3) the loading associated with normal fetal muscle development, which is movement dependent.

The Utah paradigm, therefore, predicts that bone strength and, thus, bone density and bone architecture are directly related to fetal movement. In situations in which there is diminished fetal movement, decreased bone strength of the fetus and newborn is expected through changes in bone density and bone architecture. Three observations support the hypothesis that fetal movement determines fetal bone strength. First, previous work by Rodriguez et al. ⁽²¹⁾ showed that infants with congenital neuromuscular disease in which there is both decreased fetal movement and decreased fetal muscle mass and function have osteopenia and decreased cortical bone thickness of long bones compared with controls. This observation suggests that there is diminished subperiosteal bone formation in infants with prenatal-onset neuromuscular disease. Second, Rodriguez et al. ^{(22, 23)} also described an experimental animal model called the fetal akinesia deformation sequence in which rat fetuses are pharmacologically immobilized with curare at 17 d of gestation (term gestation is 21 d). At birth, these curare-exposed rats have short umbilical cords and osteopenia compared with controls. Decreased fetal movement leads to a short umbilical cord ⁽²⁴⁾. Third, diminished fetal movement and intrauterine confinement have been put forth as the underlying basis of temporary brittle bone disease ^{(25, 26)}. This observation has suggested that prenatal bone loading in the form of fetal movement can influence postnatal bone strength during the first year of life and that infants who had significantly decreased fetal movement may be at risk for incurring fractures with physical forces that might not ordinarily cause a fracture, especially in the first 4 mo of life. Preterm birth is overrepresented in infants with temporary brittle bone disease ⁽²⁵⁾.

APPLICATION OF THE BIOMECHANICAL MODEL OF BONE FORMATION TO THE BONE DISEASE OF PRETERM BIRTH

That the fetus has a functioning musculoskeletal system by 16 wk of gestation sets the backdrop for the influence of biomechanics on fetal bone development after 16 wk of gestation. Whereas genetic information, hormonal influences, and nutrient considerations all influence bone physiology after 16 wk of gestation and into postnatal existence, it is biomechanical considerations that primarily determine ultimate bone strength, and these considerations have not been fully appreciated in the past in models of bone physiology before the Utah paradigm.

The extent of in utero bone loading will determine the ultimate skeletal strength of the fetus, especially during the last trimester, when there is rapid bone growth and bone mineralization. Fetal movement in the third trimester is the critical event that endows the newborn infant with normal bone loading and, thus, normal skeletal strength. The term infant who has an intact neuromuscular system realizes the full influence of this fetal movement on bone formation. The intrauterine loading of the fetal musculoskeletal system through fetal movement activates the mechanostat to increase bone strength through the process of modeling as shown in Fig. 2. Fetal movement also promotes muscle growth, which contributes to bone loading and thus also influences bone modeling.

When an infant is born markedly preterm, however, the infant is deprived of much of this musculoskeletal bone loading in utero as also shown in Fig. 2. After birth, the markedly preterm infant is often hypotonic and has a poverty of movements compared with the term infant ⁽²⁷⁾. Attenuated bone loading in the VLBW, preterm infant leads to an input strain to the mechanostat that is lower compared with the term infant. Thus, there is also postnatal modulation of the mechanostat to increase resorption and decrease bone formation in the VLBW, preterm infant compared with the term infant. The markedly preterm, VLBW infant is, therefore, at a distinct biomechanical disadvantage in bone formation by losing weeks of meaningful intrauterine movement that promotes bone formation and replacing this period with that of an earlier-than-expected encounter with the extrauterine environment, which is less favorable for bone formation.

The rib fractures associated with preterm birth have the same underlying cause as the long bone fractures. The bone loading of ribs probably can occur from the following:1) fetal movement and kicking that likely is transmitted along the skeleton to the ribs;2) active or passive breathing, which would provide some bone loading through the ribs expanding in inspiration and contracting in expiration; and 3) the muscles attached to the ribs, which indirectly would get stronger with active breathing but probably would not get stronger if breathing were assisted by mechanical ventilation. Thus, a term infant who benefited from the loading of the skeleton during the entire 40 wk of gestation and who was actively breathing and not ventilator dependent during the newborn period would have stronger ribs than the 28-wk preterm infant who was deprived of 12 wk of exuberant intrauterine bone loading and who was on a ventilator for a prolonged period after birth because of respiratory problems. Rodriguez et al. ⁽²¹⁾ found that the periosteal diameter of the fifth rib in infants with prenatal-onset neuromuscular disease was significantly lower than that of control infants, which indicates that prenatal bone loading does influence rib strength.

The recently published study by Moyer-Mileur et al. ⁽²⁸⁾ provides support that bone loading is important in bone formation of the preterm infant. They found that preterm infants who received daily physical therapy for an average period of approximately 27 d after birth had gains in forearm bone mineral density that were 75% greater than those in infants who did not receive physical therapy. This daily physical activity mimics the movement that this born, preterm infant would have had as an intrauterine fetus if the infant had not been born preterm.

The traditional, biochemical paradigm of bone biology adequately details the intricate relationships between calcium, phosphorous, and various other hormonal influences on their disposition, as shown in Fig. 1A. However, the biochemical model does not consider the primary determinant of bone formation, bone loading. Only when biomechanical factors are considered in the context of the biochemical model of bone biology is there a complete picture of bone dynamics as shown in Figure 1B. This biomechanical model of perinatal bone formation suggests that mineral availability needs to be matched for the degree of bone loading on the skeletal system of the fetus/infant. Intrauterine movement of the fetus in the last trimester is much greater than the movement of the newborn infant, term or preterm, in the immediate postnatal period. The intrauterine environment is unique and well-suited for promoting bone loading of the fetal musculoskeleton, for the fetus is buoyed in amniotic fluid, which allows for bouncing and kicking against the uterine wall. This type of environment cannot be duplicated once the infant is born; thus, the VLBW, preterm infant loses this critical period of intrauterine bone formation.

This model predicts that the amount of mineral needed for bone formation would be less once the infant is born, because of the change in the quality and quantity of movement, yet it has been the goal to attain in the VLBW preterm infant mineral availability that is comparable to the in utero delivery of calcium and phosphorus. The conventional wisdom of trying to achieve the same levels of mineral availability in the immediate postnatal period should be reevaluated for it may not be physiologically adaptive to the level of bone loading. The lower concentrations of calcium and phosphorus in breast milk may be giving us this message.

The biomechanical model of bone formation also explains the observations that chronic illness, bronchopulmonary dysplasia, and hyperalimentation are associated with the bone disease of preterm birth. All of these are associated with relative immobilization compared with a healthy, term infant and therefore would lead to increased bone resorption. The decrease in calcium accretion between 35 and 40 wk of gestation also follows from the biomechanical paradigm, because there is a physiologic crowding of the fetus during this time, with a rapidly increasing fetal volume and decreasing amniotic fluid volume ⁽²⁹⁾.

This biomechanical paradigm has important therapeutic implications in the treatment of the bone disease of preterm birth. In addition to the amounts of calcium and phosphorus in the diet of the VLBW, preterm infant, attention should be given to the bone loading of these infants. Passive range-of-motion activities should be considered in these infants, the success of which has been demonstrated by Moyer-Mileur et al. ⁽²⁸⁾. The frequency of nephrocalcinosis, which is associated with VLBW infants, might be decreased with this approach, as it would increase bone accretion and thus decrease the amount of calcium presented to the kidney ⁽³⁰⁾.

CONCLUSION

Fetal bone accretion is directly related to fetal movement. Although nutritional factors such as mineral availability may be contributing factors in the bone disease of preterm birth, this condition is best explained by the decreased quality and quantity of intrauterine and extrauterine movement of the VLBW, preterm infant compared with that of the term infant. Some of the problematic issues of the bone disease of preterm birth and rational therapeutic interventions for its treatment become readily understandable with a biomechanical perspective of this issue.

Source:

http://journals.lww.com/pedresearch/Fulltext/2003/01000/The_Bone_Disease_of_Preterm_Birth__A_Biomechanical.5.aspx#

Hypothesis: Fetal Movement Influences Fetal And Infant Bone Strength

Marvin E. Miller

Received 21 April 2005; accepted 12 May 2005. published online 01 August 2005.

Summary

Handheld Fetal Movement Tracker

Infants who present with multiple unexplained fractures in which there is no prior trauma, no radiographic evidence of metabolic bone disease, and no biochemical evidence of metabolic bone disease are almost always diagnosed as victims of child abuse, even though parents and caregivers deny wrongdoing. Such a diagnosis has far reaching implications for the infant and family. This article describes the clinical features of 65 such infants with multiple unexplained fractures in which the parents and caregivers deny wrongdoing and in which child abuse was diagnosed. These infants have the phenotype of temporary brittle bone disease that was described by Paterson. A striking observation in these young infants is the pregnancy history of decreased fetal movement. A hypothesis is suggested as an alternative explanation for the mechanism of these fractures in these infants – namely temporary brittle bone disease from fetal immobilization. This hypothesis states that fetal bone loading through fetal movement is essential for the formation of bones of normal strength. This hypothesis is an application of Frost’s mechanostat/bone-loading model of bone physiology to the prenatal period of bone formation. This hypothesis explains many of the other observations about temporary brittle bone disease including the early onset of the fractures in the first several months of life, the lack of bruising, the lack of other internal organ injury, and the low risk profile of many of the parents for committing child abuse.

Source:

http://www.medical-hypotheses.com/article/S0306-9877%2805%2900259-8/abstract

NOTES ON THE CLINICAL SIGNS OF INFANTILE RICKETS AS OBSERVED IN VIENNA

THE CANADIAN MEDICAL ASSOCIATION JOURNAL

H. P. WRIGHT, M.D.

Montreal

1924

All recent clinical investigation has emphasized
the difficulty of establishing a standard
for the diagnosis of rickets. Moreover when
signs are definite the stage of the disease is
difficult to determine and for this x-ray plates
are almost essential. Cases are frequently seen,
in young infants, where marked clinical stigmata
are associated with an x-ray picture showing
the bone lesions nearly healed.
In the Vienna experience, which was concerned
exclusively with infants under 18
months, craniotabes, beading of the ribs and
cranial bossing proved the most reliable signs
of early rickets.
Craniotabes is by most writers believed to be
a rachitic change. Holt and Howland state
that it occurs in infants under six months of
age; that it is a rachitic manifestation, and depends
in no wise upon syphilis. Hess and
Meyer (1922) are of the opinion that on account
of the many qualifications with which
it is attended, craniotabes must be regarded as
an unreliable sign of rickets. In young infants
under three months there i, the difficulty, insurmountable
in many cases, of differentiating
it from the cranial softening of the new born,
which is not truly rachitic. They consider it
has its greatest significance after six months
of age.
Hughes inclines to the view that craniotabes
is always a sign of rickets and divides this
sign into (1) foetal, and (2) infantile craniotabes.
Dalywell and Mackay are of the opinion
that the presence of craniotabes supervening
after birth can in practice be accepted as evidence
of rickets. The possibility of confusion
with congenital softening is a very real difficulty,
but in the experience of these writers
the distribution of the softening is somewhat
different. Congenital delayed ossification, especially
in premature babies, was not infrequent,
and affected particularly the vertex of
the skull between the anterior and posterior
fontanelles, as well as all sutures. Craniotabes
usually appeared first as a patchy softening
along the occipito-parietal sutures. The vertex
of the skull was not usually involved, but it was
common to find all sutures abnormally pliable.
In the most severe cases seen, the whole
cranial vault was affected and a large part of
it was of ru-bber-like consistency. The distribution
was uisually a-symetrical which is another
point of difference from congenital softening;
the opinion is widely held in. Vienna that it is
more extensive on the side on which the infant’s
head habitually rests.
The acceptance by the writers of craniotabes
as a sign of active rickets is based on the following
evidence:-
(a) The seasonal incidence of craniotabes
corresponded with that of rickets.
(b) The majority of young untreated infants
with craniotabes also developed other signs of
rickets.
(c) Young infants with radiographic evidence
of active rickets usually had craniotabes
as well. (Of twenty-four infants under twelve
months with radiographic evidence of rickets,
twenty-one had craniotabes).
(d) Therapeutic test, cleared up quickly
under treatment.
The absence of craniotabes in older children
with active rickets is probably due to an alteration
in the rate of growth of different bones;
possibly craniotabes is especially likely to develop
in any youmg rachitic infants.

In the experience of these writers craniotabes
was usually the earliest sign of infantile rickets
in Vienna and could sometimes be diagnosed
before three months of age. It is a less subjective
sign than minor grades of beading, and
its persistence denotes active rickets. Though
frequently present in infants between nine and

thirteen months of age associated with rickets
of moderate severity its absence after nine
months of age is of no diagnostic significance.
Rachitic Rosary, an enlargement of the costoclhrondral
junction is an important sign of early
rickets but less easy to determine than craniotabes.
A minor degree of beading was practically
universal and in order to determine its
significance histological examination was made
of cases in the post-mortem room. Section of
the ribs showed that histological evidence of
rickets was sometimes present without enlargement
of the costo-chondral junctions; that
lesser grades of beading were frequently
rachitic but might be associated with other abnormalities
such as osteoporosis, and that the
more marked enlargements were either rachitic
or scorbutic in, origin. The rachitic rosary is
usually developed later than craniotabes. It
was commonly seen in the fifth to the sixth
nonth of life. A rapid rate of enlargement
proved very significant although eventually responding
to treatment. Diminution in size was
not manifest for from four to ten weeks by
which time by x-ray calcification could be
shown to be far advanced.

Cranial bossing is not easily diagnosed in infants
of mixed races. As an early slight sign
it is not of much value, but when associated
with other early signs it is helpful in early
diagnosis.

Epiphyseal Enlargement-is a later sign than
either craniotahes or the rachitic rosary and is
of little valuie in indicating the onset of the
disease. Radiographic evidence of rickets at
the epiphyses can usually be demonstrated be-
Nasal Operations in Bronchial Asthma.-In
analyzing ninety-four consecutive cases of
bronchial asthma that have been under his personal
observation for a number of years, Morris
H. Kahn, New York, had the opportunity to
notice the effects of nose and throat operations
on thirty-three of these. In fifteen cases, relief
of nasal obstruction was obtained. In two
of these, atrophic rhinitis resulted as a serious
sequel. In the other cases, the operation was
fore the development of any enlargement by
clinical examination.
Towards the end of the first year of life some
increase in the size of the wrist and ankle occurs
in normal limbs and complicates the diagnosis
of rachitic enlargement. When enlarged
epiphyses are present their-significance can only
be interpreted in association with other clinical
signs or radiographic evidence, as the enlargement
persists long after the active stage of the
disease is past.
Delayed closing of fontanelles is frequently
m!et with in rickets and is sometimes present in
cases with no signs of rickets and in some
definite cases of rickets the fontanelles closed
at an early age. Thoracic deformity is a secondary
defect from mechanical stress, etc. Curvature
of long bones is not an early sign.
As regards the signs of rickets other than
the bone lesions, it is a matter of observation
that they vary considerably in individual cases.
Shipley, Park and others have suggested recently
that different clinical and histological
pictures of rickets may develop as the ratio of
calcium to phosphorus is varied in the diet.
Rickets has been subdivided into two groups-

(1) Rickets with low blood calcium and normal
phosphorus; (2) Rickets with low blood phosphorus
and normal calcium.
Such an explanation might explain the high
incidence of tetany (low calcium) in Glasgow
where 40%c of cases of rickets showed tetany,
while in Vienna tetany as a complication was
comparatively rare. Pallor, sweating of head,
enlargement of spleen and anaemia were not
noted to be more marked than in non-rachitic
infants.

Source:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1707463/pdf/canmedaj00439-0082.pdf

Infantile Rickets: A Mothers Struggle For Her Daughter

On June 3, 2010 my five and a half week old daughter was introduced to the Child Protection Team in a hospital in a local hospital’ by diagnosing her as being a victim of child abuse. I brought my new born daughter to the hospital, after she woke up screaming in pain when i moved her arm. Upon multiple x-rays we found out that she had a fracture in her right arm that had a transverse configuration, without any evidence of external injury (we later learned that a transverse configuration is a typical fracture morphology in a pathologically fragile bone). Not understanding how this could have happened to my daughter, my boyfriend and I had no explanation for the injury.

Apparently because of the injury and our inability to explain how it happened, the doctors at the hospital suspected child abuse and contacted Child Protection Services (not the actual name of the agency) who sent social workers to the hospital to interview us. After several hours of questioning, they transferred us to another hospital.where we were immediately admitted to the Child Protection Department. After further x-rays and bone scans the hospital found multiple micro fractures throughout my daughter’s body, and a slight bilateral subdural hematoma.

My daughter’s initial physical examination revealed an asymptomatic child. She did not have any lesions, rashes, bruises, no external swelling, not a mark on her. The hospital did not conduct a careful assessment of my daughter’s physical condition or of my clinical and social history. They assessed her vitamin D levels which were low-normal, but not mine; they did not question me about my nutrition during pregnancy or my delivery. They did not take into consideration that I called her pediatrician on two separate occasions with medical concerns; one being that she had severe clicking in her shoulders which we later learned is due to joint laxity, a symptom of Rickets or that she had broken blood vessels in her right eye. Also knowing that I was breast feeding, he told me to stop drinking milk “stating that humans are the only other mammal to drink other mammal milk, which is not right” and he felt that me drinking milk contributed to my daughters gas discomforts. The pediatrician’s office told me these were “NORMAL” occurrence’s and not indicative of a need for a medical work up. Both hospital’s did not act in an unbiased and reflective manner or take into consideration the totality of evidence. Instead, without conducting a complete evaluation, they quickly diagnosed my daughter as a victim of inflicted injury.

Mother Painfully Faces Her Daughters Empty Crib Daily

On June 4th my five and a half week old daughter was taken out of my care and placed in the state foster care system. Upon being involved with the child protection agency, the State appointed my daughter an attorney. Attorney S, has become an angel for my daughter and to my family. Thankfully, Attorney S took her job seriously and set out to determine the truth of what happened to my daughter.

After interviewing me and my family and reading the transcripts of the initial interviews of my boyfriend and I written by the emergency social workers from the hospitals, Attorney S requested all of the x-rays, bone scans and medical reports from both hospitals.

Attorney S asked several doctors to look at the medical information and give their unbiased, expert opinions who refused to touch the case because the hospital in question is very reputable. Thankfully, she finally reached out to Dr. Patrick Barnes, a world-renowned neuroradiologist who agreed to look at my daughter’s case. He referred Atty S to Dr. David Ayoub a diagnostic Radiologist out of Chicago IL, to look at the xrays and bone scans specifically. After an initial review of the films, Dr. Ayoub proceeded to acquire every medical record in existence on my daughter including my prenatal records and ultrasounds, my daughter’s delivery and pediatric records and he had me fill out a medical questionnaire survey.

After careful and thorough review of ALL medical reports he saw that my daughter was suffering from a metabolic bone disease which he diagnosed as INFANTILE RICKETS in the state of healing, and that her bones were in a fragile state. He also stated that my daughters skull showed poor mineralization along the sutures and large areas or poor mineralization in the center portion of the skull plates. In addition the parietal skull was flattened.

Dr. Michael Holick

As Dr. Ayoud was evaluating my daughters medical reports, he aksed Atty S to suggest that I go see Dr. Michael Holick, a world renowned endocrinologist. Upon his full evaluation of me, Dr. Holick found me to be suffering from Osteomalacia, essentially the adult form of Rickets, and also possibly Elhers Danlos syndrome which is a genetic deficiency that cross ties to my daughters metabolic bone disease.

This process took two months to complete and now, because of the lack of follow through by multiple health care providers including the Doctors at the hospital, my daughter has been without one of the things most critical to her young development, a caring and loving mother. And I have been robbed of some of the most precious moments I could have had with her.

Because it took so long to get the proper diagnosis and after being in foster care for almost two months, the child protection agency then decided to place to my daughter with her biological father who abandoned us when I was 2 months pregnant. He had not seen or even asked about his daughter until he was contacted by the child protection agency on June 4th, almost six weeks after her birth.

It has now been 3 months since I have had my precious baby girl. Even with two outstanding doctor reports from two nationally distinguished doctors, the child protection team doesn’t seem to care that my daughter was taken from her mother in error. Because the child protection agency is essentially a body of law in itself, they have no legal obligation to take this new medical information about my daughter and myself and do anything with it.

It would take pages to explain the twisted system that is child protection services but this system is set up in such a way that there actually isn’t a forum to bring this new information up in front of a judge unless the whole case goes to a trial, which would be months away.

This child protection agency and all child protection agencies were set up to protect children, which I totally respect, but where are the laws set up to protect the children and families from these agencies? What do you do when the Doctors and the the child protection agencies are the ones responsible for Neglect or Abuse?

Still to this day neither the child protection agency, or my daughters biological father have taken my daughter to get looked at by a specialist, to make sure that she is getting what she needs to fix her deficiency. (Thankfully, Dr. Ayoub assures me that because she has been fed formula since she was removed from my custody, I exclusively breast-fed her for the first 5 weeks, another risk factor for rickets, she is most likely safe from further fractures.) I am not allowed to get any medical information about my daughter as her bio dad has temporary custody. He is only allowing me to see my now 4-month-old daughter one day a week, at a supervised visitation center. In what kind of world does any of this seem right?

I will get her back, it will just take some time. I just hope that other families and children can be saved by being made aware of this epidemic. Health care providers need to be educated on these issues. Most doctors are not taught to know what to look for when they are dealing with rickets or other metabolic bone diseases. And when Neonatal Ricktes are in the stages of healing the vitamin D and calcium levels are usually normal or high. That’s why it’s important to test, everything !!! They need to do their due diligence in ruling out EVERY medical possibility before making their diagnosis’s. They need to help save families, not help break them up.

Addendum From Medical Misdiagnosis:

This mother has courageously started an informational Facebook page and we would urge the readers support this and to forward this information onto others.

http://www.facebook.com/pages/Rickets-an-Epidemic/153700587976477?v=app_2373072738&ref=ts#!/pages/Rickets-an-Epidemic/153700587976477

Metabolic Bone Disease Vs. Inflicted Child Abuse

Multiple Fractures from Metabolic Bone Disease, being Falsely Attributed to Inflicted Child Abuse

One of the defining differences between traumatic fractures and those of metabolic origin is a prevalence of shearing, severance, and/or major dislocations in fractures of traumatic origin as compared with their absence or rarity on those of metabolic origin.(1) A second defining difference is the absence of pain and discomfort in metabolic fractures. Traumatic fractures, in contrast, are almost always extremely painful. This is easily explained. It is well known that bone has no pain fibers, while surrounding connective tissues are abundantly supplied with pain fibers. In metabolic fractures, which can take place with ordinary infant handling, surrounding connective tissue is not involved. In traumatic fractures, surrounding connective tissues are torn resulting in significant pain, as anyone who has experienced a sprained ankle or traumatic rib fractures can testify.

Current Standards of Medical Practice Concerning Multiple Fractures, and the Requirement for Differential Diagnosis

As reported by Jenny C, Committee on Child Abuse and Neglect, in “Evaluating infants and young children with multiple fractures,” Pediatrics,(2)(2006), a differential diagnosis of child abuse should include the following list, with appropriate evaluation for each, according to currently recognized medical standards. Anything less should be
considered as substandard medical practice.

‘ Osteogenesis imperfecta
‘ Preterm birth (osteopenia of prematurity)
‘ Rickets
‘ Osteomyelitis
‘ Copper deficiency
‘ Disuse demineralization from paralysis
‘ Other rare conditions (e.g. Menkes Syndrome)

Two additions might legitimately be added to this; First, classical scurvy from vitamin C was characterized by multiple fractures. Vitamin C deficiency is still quite prevalent and may be a contributory factor in many cases of brittle bone disease. This is due to the essential role of vitamin C as an enzymatic cofactor for the conversion of the amino acid, proline, into procollagen and collagen tissue, the latter making up 90 % of bone mass. (3) Second, based largely on the pioneering work of Marvin Miller (reviewed below), disuse demineralization of bone will take place in any situation involving prolonged immobilization of bone. This is well documented in children with club feet subjected to prolonged immobilization in corrective casts, as well as in animals sent into the weightlessness of space in early experiments by the Soviet Union. As a matter of common observation, it may be a complication of prolonged bed rest. Finally, the immobilization of the fetus from any cause during the last trimester of pregnancy may result in “temporary brittle bone disease,” according to the work of Marvin Miller. (Emphasis added) Flawed Medical Consensus that Multiple Fractures in Infants, in the Absence of Known Accidental Trauma, are Diagnostic of Child Abuse

In 1990 Garcia reported in Journal of Trauma on a series of 33 children brought into a trauma center with rib fractures, all brought about by blunt trauma. Nearly 70 percent were from auto accidents, 21.2 percent from child abuse, and 9.1 percent from falls. Mortality was 42 percent. 72 percent of the children with three rib fractures had internal chest injuries, such as lung punctures or tears and/or injuries to other internal chest organs. With four or more rib fractures there were 100 percent internal chest injuries. (1) By way of explanation, when rib fractures are brought about by severe blunt force, such as in auto accidents or falls, a significant portion of ribs will be severed and sheared, the severed pieces acting like spears that are plunged into the deeper chest organs. In the present series of 30 infants, there was only one report of internal chest injury (pleural effusions). From a statistical standpoint, this small incidence would have been a virtual impossibility, had these fractures resulted from violent, inflicted force.

Atrophy of Disuse as Applied to Fetal Bone Development: Spontaneous Fractures Taking Place during Childbirth or the Neonatal Period, Commonly Attributed to Child Abuse

Atrophy-of-Disuse is a universal principle as applied to human organs, tissues, and physiology. Bone is no exception. Common examples include bone weakening and rapid decalcification known to take place during prolonged bed confinement, thereby predisposing to spontaneous fractures or fractures with minimal trauma. As reported by Grayev et al, eight children with clubfeet experienced metaphyseal fractures during physical therapy when their legs were passively manipulated, their legs having been immobilized for prolonged periods in corrective casts. (4) In studies by Rodriguez et al of the long bones in newborn infants with congenital muscular dystrophy (with marked muscle weakening/paralysis), the bones were found to be thin, hypomineralized, and elongated. In most of the bones there were multiple diaphyseal (shaft area of bone) or metaphyseal (at ends of bones) fractures or both. (5, 6) A study of rat fetuses that were curarized (paralyzed) during the later phases of pregnancy revealed marked thinning and delay in ossification of bone.(7) Conversely, as a matter of common observation, exercise such as weight lifting strengthens bone as well as muscle, or else stress fractures would be near universal in more advanced weight training.(8,9)

The following paragraph from the text, Skeletal Tissue Mechanics, by R Martin et al,(1998) vividly describes the “atrophy of disuse” process as applied to bone: “It is commonly observed clinically that the intact portions of the fractured bone become osteoporotic as healing occurs. This generalized osteopenia of the intact regions, called posttraumatic osteoporosis or posttraumatic bone atrophy, is caused by two factors. First, in addition to the healing response, the fracture causes a remodeling….so that osteonal BMUs riddle the entire cortex with resorption cavities.

The second factor is the removal of mechanical loading from the fractured bone…If the fracture is well fixed and sufficient loadbearing is resumed, the resorption spaces will refill and the osteopenia will be transient.”(10) In other words, without movement or weight bearing, such as takes place when a fractured limb is immobilized in a cast, there may be significant decalcification of the bone; but there will be rapid recalcification once movement, weight bearing, and other mechanical stresses of daily living are resumed. With the above material as background, one of the frequent causes of osteopenia with spontaneous fractures during the perinatal period (shortly before and shortly after birth)  is prematurity. (11-13) As reviewed by Marvin Miller, (12)(2003), premature infants are at increased risk to develop temporary brittle bone state. It has traditionally been thought that the primary cause was insufficient calcium and phosphate in the diet of the premature infant. However, there is emerging evidence that the bone disease of prematurity may be more of a mechanical issue than one of nutritional mineral deficiency. Miller suggested that this increased bone resorption in the premature infant compared to the term infant is secondary to inadequate “bone loading” in the form of fetal muscular movement. During the last trimester of a full-term pregnancy the fetus is actively kicking and bouncing against the mother’s uterus. This fetal activity with associated muscle development is the
primary determinant of fetal bone formation, without which the bone remains poorly ossified, weak, and brittle.
It has been shown that preterm infants who receive 5-10 minutes of daily physical activity, with passive movements of extremities by nurse attendants, realize a 76% greater gain in bone density by one month of life compared to control premature infants who receive no physical activity. (8) M. Miller and T Hangartner have observed a comparable clinical situation referred to as “temporary brittle bone disease” associated with lack of fetal movement during the last
trimester of pregnancy, in which the baby remains susceptible to spontaneous fractures with minimal trauma for 6 or more months following birth.(14- 15)(Emphasis added) Risk factors that may lead to reduced fetal movement from limited uterine confinement include twin or triplet pregnancies, cephalopelvic disproportion, oligohydramnios (reduced amniotic fluid), large maternal uterine fibroids, or other maternal structural uterine abnormalities. Fetal structural defects such as clubfoot and dislocated hips may also result in decreased fetal movement; also short umbilical cords (16) and depressive-type drugs taken by the mother during pregnancy. (17)

Radiology Interpretations:

It is likely that many cases of metabolic bone disease are being missed in hospitals for the following reason: In the earlier phases of metabolic bone diseases, x-ray studies are of limited value since there must be at least a 30 to 40 percent loss of bone density (calcification) before there is any detectable reduction of whiteness on the films,(18-21) a level at which fractures may take place with minimal trauma or ordinary infant handling, (a physiology unknown to many prosecutors.)

Congenital Rickets from Vitamin D Deficiency

It is well established that there is a re-emergence of vitamin D-deficient rickets with “an alarming prevalence of low circulating levels of vitamin D in the United States population, leading to an increased incidence of infant fractures, especially when premature.” These conclusions were announced by the National Institute of Health (NIH) following a conference on vitamin D, October 9-10, 2003.(22) In a study conducted at the Pittsburgh Graduate School of Public Health, (23)(2007) serum 25-hydroxy vitamin D was measured at 4-21 week gestation and predelivery in 200 white and 200 black pregnant women and in cord blood of their neonates. Over 90 percent of women used prenatal vitamins. Women and neonates were classified as vitamin D deficient at less than 37.5 nmol/LI, insufficient between 37.5 and 80, and sufficient at over 80. At delivery, Vitamin D deficiency and insufficiency occurred in 29.2% and 54.1% of black women and 45.6% and 46.8 of black neonates, respectively; 5 % and 42.1% of white women and 9.7% and 56.4% of white neonates were vitamin D deficient and insufficient respectively. In other words, over 92% of black neonates and 66% of white neonates were born with grossly deficient or suboptimal vitamin D levels. It was concluded that black and white pregnant women and neonates residing in the northern USA are at high risk of vitamin D insufficiency, even when mothers are compliant with prenatal vitamins. Causes of the reemergence include reduction in milk intake (milk allergies, lactose intolerance, reduction in vitamin Dcontaining fats, and increased use of sun screens (sun acts on skin oils to generate vitamin D precursors).
An article entitled, “Rickets vs. Abuse: A National and International Epidemic,” by Kathy Keller and Patrick Barnes,(24)(2008) provided a review of the literature and four case reports of infants with multiple fractures demonstrating classical x-ray findings of rickets. Also, in each case vitamin D deficiencies were documented in the mothers. Classical x-ray findings of congenital rickets include the following:

Washed-out appearance of skull from side view.
Skull sutures widened and irregular.
Pseudo fractures occur in weakened bone with normal infant handling.
Rachitic rosaries: (Bulging irregularities in the growth centers at the anterior ends
of the ribs.)
Irregularities of the paired forearm bones at their endings in the wrists.
Curved diaphyses of leg bones (“bowed legs”) even before walking.
Absence of dense white lines in growth centers of epiphyses, such as at the wrists.
Maternal and infant diet histories are of highest importance in these cases.

Nutritional rickets has also been described with normal circulating 25-hydroxy vitamin D attributed to calcium deficiency in infants.(20) Elevated parathormone (PTH) levels are generally found in these cases.

Infantile Scurvy (Barlow’s Disease)

Infantile scurvy is another possible cause of spontaneous fractures, which may be more common than generally appreciated. The probability of Barlow’s Disease can be increased by maternal malnutrition, by hyperemesis gravidarum (excessive vomiting in pregnancy), by viral or bacterial infections in the mother or the infant. (26) The bones of infants may be vulnerable to fracture and defective formation before radiological signs appear. (18-21) Scurvy or subclinical scurvy would contribute to the deficiencies of proline and lysine hydroxylase (amino acid enzymes) that affect connective tissue components of bone formation. The hydroxylation (oxidation) of proline and lysine into procollagen is carried out by the enzyme prolyl hydroxylase, which requires vitamin C as a cofactor. (27,28) Collagen provides the bone’s tensile strength, comprising 90 percent of bone matrix. Deficiencies in vitamin C would compromise the prolyl hydroxylase enzyme system, resulting in imperfect bone formation. Far from being uncommon, vitamin C deficiency does still commonly occur in the Western World. When people attending a Health Maintenance Organization (HMO) in Tempe Arizona were tested for plasma vitamin C, it was found to be depleted (between 0.2 and 0.5 mgs/100 ml) in 30 percent and deficient (below 0.2 mgs/100 ml) in 6 percent. (29) As reviewed by Clemetson, when the human plasma ascorbic acid level falls below 0.2 mg/100 ml, whole blood histamine level is doubled or quadrupled. (30) It has been shown that bleeding from scurvy results from increased blood histamine, or histaminemia, which causes separation of endothelial cells from one another in capillaries and small venules, leading to spontaneous bruising. (31) When these are seen by a physician, almost always inflicted abuse is erroneously suspected. It follows then that the diagnosis of non-accidental trauma based on multiple bruises cannot be ethically or professionally justified without first ruling out scurvy by a plasma vitamin C blood test.

Metabolic Bone Disease and Vitamin K Deficiency

Maternal vitamin K deficiency during pregnancy is a risk factor for hemorrhagic disease of the newborn (HDN), usually a self-limited disorder taking place within 24 to 72 hours following birth. The primary dietary source of vitamin K is from green, leafy vegetables. It is for this reason that a maternal dietary history is of highest importance in adequate evaluation of infant fractures. Although calcium absorption from the gut into the blood stream is dependent on vitamin D, it is less well known that vitamin K delivers calcium from the blood into the bone.(32) Consequently deficiencies of vitamin K in early infancy may be a contributory cause of metabolic bone disease. Also, bone matrix proteins necessary for normal bone metabolism are vitamin K-dependent,(33-35) so that vitamin K deficiency in infants can lead to fractures as well as hemorrhagic disease..

Osteopenia of Prematurity

As reviewed above under “Atrophy of disuse,” prematurity poses one of the most common sources of infant fractures. (11-13) This is due to the fact that the fetal kicking and other vigorous body movements, which are essential for promotion of bone strength and integrity, are only in their beginning phases when preterm births occur. These
movements are intrinsically necessary for bony maturation, just as they are necessary to maintain bone strength at all ages following birth.

In Nelson’s Textbook of Pediatrics, 16th Edition, the following quotation is found:
“Osteopenia of prematurity. Very small premature infants with chronic illnesses often develop a rickets-like syndrome with pathologic fractures and demineralized bone. There may be associated cholestasis and vitamin D or calcium malabsorption; urine calcium loss due to diuretics; and poor calcium, phosphorus, or vitamin D intake, or aluminum toxicity. The treatment of fractures requires immobilization and administration of calcium and, if needed, phosphorus (for hypophosphatemia) and vitamin D (not more than 1,000 IU/day unless severe cholestasis or vitamin D resistance). Appropriate formulas for premature infants should provide a more optimal intake of calcium, phosphorus, and Vit. D.”(36)

As reviewed by FR Greer:

“Osteopenia of prematurity refers to the hypomineralized skeleton of the premature infant compared with that of the normal fetal skeleton…..In growing, low birth-weight infants with birth weight less than 1500 grams (3.3 lbs) and less than 32 weeks gestational age, it occurs almost without exception. This high incidence (of hypomineralization) is not surprising considering that 80% if fetal skeletal mineralization takes place during the last trimester of pregnancy. Thus one would expect an increasing degree of osteopenia in premature infants with decreasing gestational age. …Even term infants may have decreased stores owing to maternal complications such as severe preeclampsia.”(37)

Three reviews of fractures occurring during the first year of life in premature infants (38-40) found that rib fractures often remain undetected and are only discovered on x-rays taken for other reasons. In one series, clinical suspicion of fractures was documented prior to ordering the radiographs in only 3 of the 19 (16%) infants.(41) Hence the true incidence of fractures in infants born prematurely remains unknown, but it probably is much more common tan reported in the literature.

Timing of Fractures

In court cases involving multiple fractures in which parent and/or caretaker have been accused of child abuse, the dating or timing of the fracture often plays a critical role.

As reviewed by Amir et al,(11) from 1977 to 1984, 973 premature infants were admitted to the neonatal intensive care unit of Beilinson Medical Center, Petah Tiquva (Isreal). Among those who survived over 6 months, 12 suffered from fractures that appeared during their hospitalization between ages 24 and 60 days. All of these were without clinical signs. All were diagnosed on routine chest x-rays. Callus was always present when first diagnosed. In six instances angulation was present, but there were no instances of separation or dislocation in the fractures. According to the authors, fractures usually occur a few weeks after birth, and are almost always pathologic, the most
common cause being metabolic bone disease.

According to N. Bishop, who observed a somewhat different timing, fractures due to osteopenia of prematurity and preterm rickets occur typically from 10 weeks age and usually stop before 6 months.(39) In one of the earliest prospective studies of the clinical course of fractures and rickets in very low birth weight infants (less than 1,500 grams) by WH Koo et al, (13) 78 infants were enrolled solely on the criteria of birth weight <1,500 grams. There was a distribution of 82 fractures in 19 infants in the study. 73 fractures (89%) originated during the course of hospitalizations ranging from 32 to 131 days. Clinical suspicion was documented prior to ordering the radiographs in only three of the 19 infants (16%). It was further determined that physical therapy was the source of some of the fractures. Fractures from congenital rickets, when followed serially on radiographs, showed complete resolution beyond six months after birth.

Conclusions and Recommendations:

The Jenny report in 2006, which established a standard for the differential diagnosis of multiple fractures in infants and children, might justifiably be considered a major landmark in medical history. Since the publication of this report, it has been incumbent on physicians to rule out various forms of metabolic bone disease before diagnosing inflicted child abuse directed against parent or caretaker. In my opinion, failure to do this must be considered substandard medical practice, bringing disrepute on the medical profession.
According to the time-honored principle of “considered innocent until proven guilty,” appropriate medical evaluation of multiple fractures would require a formal listing of a differential diagnosis and appropriate laboratory tests. In addition to routine chemistries and blood counts, blood tests should include 25-hydroxy vitamin D, alkaline
phosphatase, parathormone, calcium, phosphorus, serum histamine, plasma vitamin C, and tissue exams for osteogenesis imperfecta. These tests should be performed immediately on finding of fractures, as later tests might be irrelevant. A careful medical history of the mother’s diet and vitamin supplements during pregnancy and of the infant’s
diet and supplements following birth are of paramount importance. Lacking these criteria, diagnosis of inflicted child abuse cannot be justified.

References

1. Garcia V, Gotschall C, Eichelberger M, Bowman L. Rib fractures in children: a marker
of severe trauma, J Trauma. 1990; 30(6):695-700.
2. As reported by Jenny C, Committee on Child Abuse and Neglect, in “Evaluating
infants and young children with multiple fractures,” Pediatrics, 2006 Sept; 118(2):1299-
1333.
3. Qutob S, Dixon S.J., and Wilson, J.X. Insulin stimulates vitamin C recycling and
ascorbate accumulation in osteoblastic cells, Endocrinology, 1998; 139(1):51-56.
4. Grayev A. Metaphyseal fractures mimicking abuse during treatment for clubfoot.
Pediatr Radiol, 2001; 31:559-563.
5, Rodriguez J, Garcia A, Palacios J et al. Changes in long bone due to fetal immobility
caused by neuromuscular disease. J Bone and Joint Surg, Aug., 1988; 70-A:1052-1060.
6. Rodriguez, JI, Palacios, J, Garcia-Alix A, Pastor I, Paniagua R. Effects of
immobilization on fetal bone development. A morphometric study in newborns with
congenital neuromuscular diseases with intrauterine onset. Calcific Tissue Intern., 1988;
43:335-339.
7. Rodriguez J, Palacios J, Ruiz A et al. Morphologic changes in long bone development
in fetal akinesia deformation sequence: an experimental study in curarized rat fetuses.
Teratology, 1992; 45:213-221.
8. Moyer-Mileur U, Brunstetter V, McNaught TP, et al. Daily physical activity increases
bone mineralization and growth in preterm very low weight infants. Pediatrics, 2000;
106:1088-1092.
9. Hangartner, TH. Osteoporosis due to disuse. Physical Medicine Rehabilitation, Clinics
of North America, 1995; 6:579-594.
10. Martin R, Burr D, Sharkey, N. In: Skeletal Tissue Mechanics, New York: Springer,
1998: 75.
11 Amir J, Katz K, Grunebaum M, et al. Fractures in premature infants. J Pediatr
Orthop, 1988; 8:41-44.
12 Dabezies E and Warren P. Fractures in very low birth weight infants with rickets.
Clinical Orthopaedics and Related Research, 1997; 335:233-239.
13 Koo W, Sherman R, Succop P et al. Fractures and rickets in very low birth weight
infants: conservative management and outcome. J Pediatr Orthop, 1989; 9:326-330.
14. Miller ME, Hangartnes T. Temporary brittle bone disease: associated with decreased
fetal movement and osteopenia. Calcif Tissue Int., 1999:137-143.
15. Miller ME. The lesson of temporary brittle bone disease: all bones are not created
equal. Bone, 2003; 33:466-474.
16. Miller, ME, Higginbottom M, Smith DW, Short umbilical cord: its origin and
relevance. Pediatrics, 1981; 67:618-621.
17. Miller ME, Temporary brittle bone disease from intrauterine exposure to drugs that
cause fetal immobilization. Calcific Tissue International, 2002; 70: 359.
18. Colbert C. The osseous system. Investigative Radiology. 1972; 7:223-232.
19. Lachman E. Osteoporosis: the potentialities and limitations of its roentgenological
diagnosis, American Journal Roentgenology, 1955; 74:712-715.
20. Greer FR. Determination of radial bone mineral content in low birth weight
infants by photon absorptiometry, Journal of pediatrics, 1988; 113:213-219.

21. Mazess RB, Peppler WW, Chesney RW et al, Does bone measurement of the
radius indicate skeletal status? Journal Nucear Medicine, 1984; 25:281
22. National Institute of Health (NIH) conference on vitamin D, October 9-10, 2003,

http://.nichd.nih.gtov/about/meeting/2003/prip_vitd.cfm

23. Bodnar LM, Simhan HN, Powers RW et al, High prevalence of vitamin D
insufficiency in black and white pregnant women residing in the Northern United States
and their neonates, Journal of Nutrition, 2007; 137: 447-452.
24. Keller KA, Barnes PD, Rickets vs. abuse: a national and international epidemic.
Pediatric Radiology, 2008; 38: 1210-1216.
25. DeLucia MC, Mitnick ME, Carpenter TO, Nutritional rickets with normal circulating
25-hydroxyvitamin D: A call for reexamining the dietary role of calcium intake in North
American infants. Journal of Clinical Endocrinology and Metabolism, 2003;
88(8):3539:3545.
26. Clemetson CAB. Is it Shaken Baby or Barlow’s Disease Variant?. J Amer Phys Surg,
2004; 9:78-80.
27. Qutob S, Dixon S.J., and Wilson, J.X. Insulin stimulates vitamin C recycling and
ascorbate accumulation in osteoblastic cells, Endocrinology, 1998; 139(1):51-56.
28. Stone N, Meister A. Function of ascorbic acid in the conversion of proline to collagen
hydroxyproline, Nature, 1962; 194:555.
29. Johnston DS, Thompson MS. Vitamin C status of an out-patient population,
American Journal Clinical Nutrition, 1998; 17:366-370.
30. Clemetson, CAB. Histamine and ascorbic acid in human blood. Journal of Nutrition,
1980; 110:662-668.
31. Gore I, Tanaka Y, Fujinami T et al. Endothelial changes produced by ascorbic acid
deficiency in guinea pigs. Archives of Pathology, 1965; 80:371-376.
32. Innis M, Vitamin K deficiency disease, Journal of Orthomolecular Medicine,
1999; 23:15-20.
33. Bugel S. Vitamin K and bone health. Proc. Nutritional Society, 2003; 62(4):839-843.
34. Iwamoto J, Takeda T, Sato Y. Effects of vitamin K2 on osteoporosis. Current Pharm
Des, 2004; 10(21):2557-2576.
35. Shirki M, Shiraki Y, Aoki C. Miura M. Vitamin K2 (menatetronone) effectively
presents fractures and sustains lumbar bone mineral density in osteoporosis. Journal of
Bone & Mineral Research. 2000; 15(3):515-521.
36. Nelson’s Textbook of Pediatrics. 16th Edition, Behrman RE, Kliegman RM, and
Jenson HB, WB Saunders Co., 2000, page 529.
37. Greer FR, Osteopenia of prematurity, Annual Review of Nutrition, 1994; 14:169-185.
38. Noble R, McDevitt H, Herbison J, et al The prevalence of rib fractures in X-preterm
infants, Bone, 2009; 45(2).
39. Bishop N, Sprigg A, Dalton A. Unexplained fractures in infancy: Looking for fragile
bones (Review). Archives Diseases of Children, 2007; 92:251-256.
40. Backstrom MC, Kuusela AL, Maki R. Metabolic bone diseases of prematurity.
Annals of Medicine, 1996; 28(4): 275-282.
41. Msomekela M, Manji K, Kazema R, Makwaya C. Annals of Tropical Paediatrics,
1999; 19(4):337-344.

Source:

http://www.progressiveconvergence.com/ShakenBaby/Multiple%20Fractures%20from%20Metabolic%20Bone%20Disease.pdf

D Deficiency – A Differential Diagnosis To Infant Fractures

Vitamin D deficiency rickets and allegations of non-accidental injury

Colin R Paterson

University of Dundee, Dundee, UK

Correspondence to Dr Colin R Paterson, Temple Oxgates, Longforgan, Dundee DD2 5HS, UK. Tel: +44 1382 360240 |

Email: c.s.paterson@btinternet.com

ABSTRACT

Vitamin D deficiency rickets has long been recognized as a cause of fractures and fracture-like appearances in young children. Often seen in the early 20th century, rickets has recently been regarded as uncommon; the radiological appearances, familiar to previous generations, may not be recognized for what they are.

This article reports four children with unexplained fractures initially attributed confidently to non-accidental injury. In each case, the later evidence of vitamin D deficiency led to a reconsideration of that diagnosis.

Conclusion:

It is important to be aware of this bone disorder in the differential diagnosis of fractures, to investigate appropriately and to recognize that the radiological appearances may be misleading. A mistaken diagnosis of abuse does real harm, not least to the child itself.

---

Received 3 February 2009; revised 26 May 2009; accepted 3 June 2009.

To View Full Article Please See Source:

http://www3.interscience.wiley.com/journal/122477279/abstract