Zone Of Provisional Calcification Research Articles

Determining normal and abnormal reference values for corrective osteotomy for congenital hand malformation: a study on the zone of provisional calcification and bone axis.

This study aims to establish reference values for the normal bone axis in children to assess the effectiveness of corrective osteotomy procedures and guide the treatment of congenital hand malformations and post-operative axis deviations. A retrospective study was carried out between January 1, 2022, and October 9, 2024. A total of 192 individuals were included. In both abnormal and normal individuals, we measured the angles within the zone of provisional calcification and the bone axis. The metacarpal, proximal, and distal phalanx of the thumb were measured in both males and females. We calculated the average and standard deviations for both groups. These normal reference values were then compared with the abnormal reference values of patients who had types II and IV polydactyly. Our work effectively established thorough reference values for the thumb's normal axis. Considering the success of corrective osteotomies in children with congenital deformities depends mostly on these values. In polydactyly type IV, we observed a change in the angle on the side with the axis deviation. Our results highlight the need for an exact preoperative design for thumb reconstruction. Italso implies the possibility of choosingthe side with little or no axis deviation during operation. This strategic selectioncan help prevent the need for additional osteotomies or subsequent surgeries. Evaluating and preparing corrective osteotomy treatments benefits significantly from the reference values for the proper alignment of the thumb's bones. These results enable surgeons to predict the degree of corrective osteotomy needed, thereby improving postoperative surgical results and patient satisfaction.

Stressed or fractured: MRI differentiating indicators of physeal injury.

To identify MRI findings that can indicate chronic physeal stress injury and differentiate it from acute Salter-Harris (SH) fracture of the pediatric knee or wrist. IRB-approved retrospective study of consecutively selected knee and wrist MRIs from 32 athletes with chronic physeal stress injury and 30 children with acute SH fracture. MRI characteristics (physeal patency, physeal thickening, physeal signal intensity (SI), continuity of the zone of provisional calcification (ZPC), integrity of the periosteum and/or perichondrium, pattern of periphyseal and soft tissue edema signal, and joint effusion) were compared. Forty-eight chronic physeal stress injuries (mean age 13.1years [8.2-17.5years]) and 35 SH fractures (mean age 13.3years [5.1-16.0years]) were included. Any physeal thickening was more common with chronic stress injury (98% vs 77%, p = 0.003). Abnormal physeal SI was more common with SH fractures (91% vs 67%, p = 0.008). ZPC discontinuity strongly suggested chronic stress injury (79% vs 49%, p < 0.004). Periosteal and/or perichondrial elevation or rupture and soft tissue edema characterized most of the acute SH fractures (p < 0.001) and were seen only in 1 chronic stress injury (< 2%). While periphyseal edema was not significantly different in the two groups (p = 0.890), a joint effusion was associated with acute SH fracture (p < 0.001). Chronic physeal stress injury of the pediatric knee and wrist shows higher incidence of ZPC discontinuity and focal physeal thickening compared to SH fracture, reflecting disruption in normal endochondral ossification. However, these findings can overlap in the 2 groups. Periosteal and/or perichondrial injury, soft tissue edema signal, and joint effusion strongly suggest SH fracture and are rarely present with chronic stress injury.

A practical approach to diagnose and treat rickets

Rickets is a disease of growing bone, before fusion of epiphyses. There is defective mineralization of cartilage matrix in the zone of provisional calcification caused either by nutritional vitamin D deficiency and/or low calcium intake or by non-nutritional causes, like hypophosphatemic rickets and rickets due to renal tubular acidosis. In addition, some varieties are due to inherited defects in vitamin D metabolism and are called vitamin D dependent rickets. The diagnosis is made on the basis of history, physical examination, and biochemical testing, and is confirmed by radiographs. Treatment consists of vitamin D supplementation as Stoss therapy or daily or weekly oral regimens, all with equal efficacy and safety, combined with calcium supplements. For renal rickets, the active form of Vit D, 1,25(OH)2 also called Calcitriol is used, treatment is tailored to another type of renal rickets. Routine supplementation starting from the newborn period is being increasingly endorsed by various international organizations. Adequate sunlight exposure, food fortification, and routine supplementation are the currently available options for tackling this nutritional deficiency. In this review article, we discuss the pathophysiology, diagnosis, and management of rickets in detail.

Is surgery always indicated in rachitic coronal knee deformities? Our experience in 198 knees.

Defective mineralization of osteoid matrix prior to physeal closure causes rickets. Poor calcification of the cartilage matrix in the zone of provisional calcification causes flattened skull, rachitic rosary, bowed legs, coxa vara and brittle bones. The recent literature has seen an increase in the incidence of the disease in both developing and developed nations. We evaluated behaviour of lower limb deformities due to nutritional rickets in 117 patients. A prospective study was conducted from January 2009 to December 2011 for clinical and radiological evaluation of knee deformities in nutritional rickets. A total of 117 patients with 198 coronal plane knee deformities between 2 years and 12 years age of rickets were enrolled in this study. In our study, there were 65 genu varum and 133 genu valgum deformities. Seven genu varum (10.7%) and 37 genu valgum (28%) deformities were regarded as failure. Fifty eight genu varum got corrected completely obtaining an average of 5° of valgum in an average of 6.3 months. The average rate of spontaneous correction was 1.9° a month. Ninety six valgum got corrected obtaining an average of 4.7 valgum in an average of 13.3 months. The average rate of spontaneous correction was 0.92° a month. Most of the rachitic deformities get corrected with age. Genu varum is having better chances and a faster rate of correction as compared with genu valgum. Early surgery may be indicated in late presenting cases. We believe varum above 4 years and 18° of valgum above 9 years usually do not correct and may require surgical intervention.

Insight into characteristic features of cartilage growth plate as a physiological template for bone formation.

Cartilage growth plate is a natural template from both a biochemical and structural point of view and allows osteoblasts migration, proliferation, differentiation, and ultimately, bone formation. It is evolutionary adjusted to support bone formation within strictly defined spatial framework serving as an interesting model for studying more mechanistically aspects which might be important for specific scaffold-based bone tissue engineering strategies. Surprisingly little is known about the geometric features of this physiological template. To this purpose we analyzed cartilage growth plate from rat, mouse, and human costochondral junction and tibia. High-resolution X-ray tomography showed that pore size in the zone of provisional calcification was within 20 to 30 µm range and in the metaphysis in 35 to 50 µm range. The thickness of calcified longitudinal septa in zone of provisional calcification was 3 to 5 µm and in metaphysis 7 to 12 µm. The porosity varied from 84 to 88%. We observed that numerical values characteristic for cartilage growth plate were not significantly influenced by the species of origin, by the type of bone, or by age. In addition, electron microscopy of calcified fragments of longitudinal septa showed that the calcium aggregates were globular, connected with each other, and formed a shell covering cartilage matrix located within longitudinal septa.

Metabolic Bone Disease in Very Low-Birth-Weight Neonates

Background: Metabolic bone diseases (MBD), including rickets and osteopenia, are important neonatal complications among preterm infants. This study aimed to determine the prevalence and risk factors of MBD in neonates with very low birth weight (VLBW). Methods: This prospective study was conducted on VLBW infants from January 2012 to July 2013. Inclusion criteria were birth weight of ≤1500 g and age of ≤7 days, and the exclusion criteria were cholestatic disorders, skeletal anomalies and genetic syndromes. Serum calcium, phosphorus and alkaline phosphatase (ALP) concentrations were measured regularly until the 12th week of birth. In addition, wrist and chest radiographs were obtained from the neonates at 8-12 weeks of age. Results: In total, 58 neonates with the mean gestational age of 30.6±2.65 weeks, weight of 1265±262 g and height of 38.06±2.49 cm were enrolled in this study. The correlation between biochemical parameters in multiple analysis and radiological findings of rickets was examined, and a significant association was observed between serum phosphorus level at the first week of age and the incidence of rickets. Moreover, 14 infants had only one radiologic sign of rickets (e.g. fraying, cupping, widening or lack of provisional zone of calcification (PZC), and 8 subjects (13.7%) showed at least two radiologic signs. The prevalence of osteopenia and rickets among infants with birth weight of 1200 g had normal X-rays (P=0.036). Conclusion: Despite the remarkable advances in the management of VLBW infants, MBD is still a prevalent complication during the neonatal period. According to the results of this study, birth weight and gestational age are the most significant risk factors for MBD.

High-resolution CT with histopathological correlates of the classic metaphyseal lesion of infant abuse

The classic metaphyseal lesion (CML) is a common high specificity indicator of infant abuse and its imaging features have been correlated histopathologically in infant fatalities. High-resolution CT imaging and histologic correlates were employed to (1) characterize the normal infant anatomy surrounding the chondro-osseous junction, and (2) confirm the 3-D model of the CML previously inferred from planar radiography and histopathology. Long bone specimens from 5 fatally abused infants, whose skeletal survey showed definite or suspected CMLs, were studied postmortem. After skeletal survey, selected specimens were resected and imaged with high-resolution digital radiography. They were then scanned with micro-CT (isotropic resolution of 45μm(3)) or with high-resolution flat-panel CT (isotropic resolutions of 200μm(3)). Visualization of the bony structures was carried out using image enhancement, segmentation and isosurface extraction, together with volume rendering and multiplanar reformatting. These findings were then correlated with histopathology. Study of normal infant bone clarifies the 3-D morphology of the subperiosteal bone collar (SPBC) and the radiographic zone of provisional calcification (ZPC). Studies on specimens with CML confirm that this lesion is a fracture extending in a planar fashion through the metaphysis, separating a mineralized fragment. This disk-like mineralized fragment has two components: (1) a thick peripheral component encompassing the SPBC; and (2) a thin central component comprised predominantly of the radiologic ZPC. By manipulating the 3-D model, the varying appearances of the CML are displayed. High-resolution CT coupled with histopathology provides elucidation of the morphology of the CML, a strong indicator of infant abuse. This new information may prove useful in assessing the biomechanical factors that produce this strong indicator of abusive assaults in infants.

Vigorous periosteal reaction secondary to copper deficiency in an infant on total parenteral nutrition

Sir, We are using this forum to share our recent experience with a 5-month-old child who had dramatic radiographic findings, in order to alert health care workers, including pediatric radiologists, about the increased likelihood of seeing copper deficiency cases in view of the scarcity of parenteral copper. Depending on the supply available, parenteral copper has been frequently omitted from total parenteral nutrition formulations in the last year or so [1]. A 5-month-old boy was transferred to our hospital for intestinal rehabilitation and evaluation for possible intestinal transplantation. He had been born at a gestational age of 34 weeks secondary to preterm labor. Prenatal US was concerning for polyhydramnios and intestinal obstruction. At birth he was found to have multiple small bowel atresias. After multiple surgeries for resections with reanastomosis, he remained dependent on parenteral nutrition and intolerant of enteral feeds. The child had been hospitalized since birth. The original chest/abdomen radiograph at our hospital showed vigorous periosteal reaction of humeri and femurs (sparing the region of the metaphysis) (Fig. 1) along with periosteal reaction of some ribs and the scapulae. Our original differential diagnoses included diffuse osteomyelitis, hypertrophic pulmonary osteoarthropathy, scurvy, vitamin D deficiency and child abuse. A bone survey then revealed osteoporosis (for example, the zone of provisional calcification of knee secondary centers could be seen better than the bone inside) and multiple metaphyseal abnormalities appearing as spurs (Fig. 2) and similar in some locations to “bucket handle” classic metaphyseal lesions of child abuse (Fig. 3). The pattern was somewhat suggestive of scurvy, a disease rarely seen in current practice. The other diagnoses considered were Menkes syndrome (kinky hair syndrome) and copper deficiency from inadequate intake. Vitamin C levels were normal, eliminating scurvy as a diagnosis. Recognition of the national shortage of intravenous micronutrients and trace elements led to evaluation of intake of copper in this boy with intestinal failure who had been dependent on total parenteral nutrition his entire life. It was discovered that because of the national shortage of parenteral copper, he had not received any copper at the referring hospital. A serum copper level showed a very low level of <10 μg/dL (normal 75–165 μg/dL), a very low ceruloplasmin level <4 mg/dL (normal 18–37 mg/dL), and alkaline phosphatase of 1,324 IU/L (normal 82–383 IU/L). Vitamin D, calcium and phosphorus levels were normal. He was anemic (hemoglobin 8.3 g/dL) on admission with normal white blood cell count. In the absence of any enteral feeds and knowledge of absence of copper in the total parenteral nutrition, the radiologic changes were attributed to acquired copper deficiency. Radiologic findings in this boy are consistent with prior reports of profound infantile copper deficiency [2, 3]. The exuberant extent of the periosteal reaction may well relate to the many weeks of normal in-patient handling of the baby without realizing he was bleeding subperiosteally. Copper deficiency leads to reduction of the activity of numerous copper-containing enzymes that are necessary for the structure and function of bone, skin, hair, blood vessels and the nervous system [4]. Children with deficient copper A. E. Oestreich (*) Department of Radiology, Cincinnati Children’s Hospital Medical Center Radiology 5031 CCHMC, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA e-mail: alan.oestreich@cchmc.org

Bisphosphonate therapy for chronic recurrent multifocal osteomyelitis

This patient was diagnosed with chronic multifocal recurrent osteomyelitis of the ankle approximately 4 years prior to the presented images. Multiple treatments were administered, most notably monthly intravenous pamidronate, a therapy that was continued for 17 months, until recrudescent disease prompted a change in therapy. At the time of the presented images, the patient had not received bisphosphonate therapy for 2 years. Bisphosphonates are a class of medications used primarily in adult patients with decreased bone mineral density. When the drug is incorporated into the hydroxyapatite matrix of nascent bone, osteoclastic activity is inhibited, and as a result, bone mineral density increases. Also used in patients with expansile bone lesions, the decrease in osteoclastic activity serves to slow the progression of enlargement, demonstrating an analgesic effect. Finally, it is thought that bisphosphonates engender a direct anti-inflammatory response by altering the inflammatory cascade [1]. In children, bisphosphonates have been used for the treatment of conditions resulting in low bone mineral density, such as osteogenesis imperfecta [2]. Furthermore, several recent studies have demonstrated the effectiveness of bisphosphonate therapy as a second-line treatment for CRMO-associated pain [3]. Most CRMO treatment regimens consist of daily infusions of IV pamidronate for 1–3 days, repeated every 3 months [1, 3, 4]. Pain relief is usually rapid, within days of initiation, and resolution of inflammation by MR imaging follows in up to 80 % of patients [2]. Radiologically, the cyclical inhibition of osteoclast activity in the skeletally immature patient gives rise to dense metaphyseal bands migrating longitudinally from the zone of provisional calcification into the diaphysis, as previously described [5, 6]. Additionally, undertubulation of the affected areas, as well a “bone within a bone” appearance can be seen [7]. The presence of metaphyseal bands engenders differential considerations such as lead poisoning and hypervitaminosis D, as well as causes of standard growth recovery lines (times of malnutrition, severe illness, etc.). As none of the causes of metaphyseal bands are common, the interpreting radiologist may be inspired to suggest further testing when confronted with this unusual finding. However, the recognition of focal undertubulation (most striking at the distal femur in this case) helps cinch the diagnosis. Recognition of these findings can be clinically important, as the abrupt change of bone mineral density at the dense bands has been implicated as a stress riser, similar to the interface between a prosthesis and native bone [8]. The potential increase in fracture risk presented by these bands may prompt a change in the duration of therapy.

Skeletal Manifestations of Scurvy: A Case Report from Dubai

Introduction. Nutritional deficiencies are rarely reported in developed countries. We report a child of Pakistani origin brought up in Dubai who developed skeletal manifestations of scurvy due to peculiar dietary habits. Case Presentation. A 4.5 year old boy presented with pain and swelling of multiple joints for three months and inability to walk for two months. Dietary history was significant for exclusive meat intake for the preceding two years. On examination the child's height and weight were below the 5th percentile for his age. He was pale and tachycardic. There was significant swelling and tenderness over the wrist, knee and ankle joints, along with painful restriction of motion. Basic blood workup was unremarkable except for anemia. However, X-rays showed delayed bone age, severe osteopenia of the long bones, epiphyseal separation, cortical thinning and dense zone of provisional calcification, suggesting a radiological diagnosis of scurvy. The child was started on vitamin C replacement therapy. Over the following two months, the pain and swelling substantially reduced and the child became able to walk. Repeat X-rays showed improvement in the bony abnormalities. Conclusion. Although scurvy is not a very commonly encountered entity in the modern era, inappropriate dietary intake can lead to skeletal abnormalities which may be confused with rickets. A high index of suspicion is thus required for prompt diagnosis of scurvy in patients with bone and joint symptoms.

Neonatal Lethal Osteochondrodysplasia with Low Serum Levels of Alkaline Phosphatase and Osteocalcin

Neonatal lethal skeletal dysplasias are rare and typically involve thoracic malformations and severe limb shortening. We report on a newborn boy manifesting an osteochondrodysplasia associated with fatal respiratory insufficiency who had normal lung volumes and extremity lengths. His disorder featured aberrant skeletal patterning and defective ossification including a severely osteopenic skull, apparent absence of clavicles, and clefting of the mandible and vertebrae. Serum alkaline phosphatase and osteocalcin levels were markedly low. Biochemical studies suggested parathyroid insufficiency probably from critical illness. Histopathology at autopsy excluded impaired mineralization of skeletal matrix, but endochondral bone formation appeared disorganized with growth plate clustering of chondrocytes in hypertrophic zones and in zones of provisional calcification. Parathyroid glands were not found. Despite features of two distinctive heritable entities, hypophosphatasia and cleidocranial dysplasia, the cumulative findings did not match either condition, and no mutations were found in either the tissue nonspecific ALP isoenzyme or core-binding factor genes, respectively, or in the genes encoding osteocalcin or the osteoblast transcription factor osterix. This patient could represent the extreme of cleidocranial dysplasia (a disorder not always associated with structural mutation in core-binding factor A1), but more likely he defines a unique osteochondrodysplasia disrupting both intramembranous and endochondral bone formation.

MRI characteristics and transverse relaxation time measurements in normal growing cartilage.

To determine the characteristics of magnetic resonance (MR) signals of normal growing cartilage and identify the difference in transverse relaxation times between physeal and epiphyseal cartilage in vivo. 24 distal femora of 12 two-week-old piglets were imaged on a 1.5 Tesla GE MR scanner. Comparison was made between signal intensity on MR images and the structure shown in corresponding histologic sections. T2 values were measured in eight piglets by means of multiecho spin-echo sequences. Our results showed that MR imaging delineated five regions between the secondary ossification center and the metaphysis, which histologically correspond to the zone of provisional calcification of the secondary ossification center, physis of the secondary ossification center, epiphyseal cartilage, physis and zone of provisional calcification. The T2 value in the physeal cartilage was much larger than that in the epiphyseal cartilage (P<0.05). It is concluded that MRI findings could differentiate the different regions of growing cartilage. T2 is longer in physeal than in epiphyseal cartilage, perhaps reflecting differences in water binding by proteoglycans.

Evaluation of 9.4-T MR microimaging in assessing normal and defective fetal bone development: comparison of MR imaging and histological findings

We evaluated 9.4-T magnetic resonance (MR) microimaging in assessing normal and defective bone development in mouse embryos. For this purpose, we performed 9.4-T MR microimaging on developing bones in normal embryos, and also in Runx2/Cbfa1−/− embryos with severely defective bone development. MR images were compared with the histological and histochemical features of these fetal bones. MR microimaging delineate successfully the normal long bone development in embryos. The T1- and T2-weighted MR microimaging demonstrated chondrocyte maturation in different regions of growing cartilage, such as epiphysis, physis, hypertrophic cartilage, and zone of provisional calcification. These developmental changes were detectable in as early as E14.5 embryos. The MR microimaging clearly demonstrated defective bone development in Runx2/Cbfa1−/− embryos. The femur from E18.5 homozygous Runx2/Cbfa1−/− embryos lacked MR signal intensity patterns including the hypertrophic cartilage, which are characteristic of the bone from the age-matched Runx2/Cbfa1+/+ embryos. Interestingly, however, the tibia from the same mutants was associated with MR signal patterns indicative of hypertrophic cartilage but not of the primary spongiosa and ossifying perichondrium, suggesting that bone development is differently regulated in these two long bones. On the other hand, the bones from heterozygous Runx2/Cbfa1+/− embryos exhibited an MR phenotype intermediate between the Runx2/Cbfa1+/+ and Runx2/Cbfa1−/− embryos; the primary spongiosa and ossifying perichondrium formation occurred normally even in the absence of preceding organized maturation of chondrocytes, a phenotype that was not detected by histological examinations. We concluded that MR microimaging is useful in assessing the bone development.

The acrophysis: a unifying concept for understanding enchondral bone growth and its disorders. II. Abnormal growth.

In order to discuss and illustrate the effects common to normal and abnormal enchondral bone at the physes and at all other growth plates of the developing child, the term "acrophysis" was proposed. Acrophyses include the growth plates of secondary growth centers including carpals and tarsals and apophyses, and the growth plates at the nonphyseal ends of small tubular bones. Abnormalities at acrophyseal sites are analogous to those at the physeal growth plates and their metaphyses. For example, changes relating to the zone of provisional calcification (ZPC) are often important to the demonstration of such similarities. Lead lines were an early example of the concept of analogy from abnormality due to physeal and to acrophyseal disturbance. The ZPC is a key factor in understanding patterns of rickets and its healing. Examples (including hypothyroidism, scurvy and other osteoporosis, Ollier disease, achondroplasia, and osteopetrosis, as well as the family of frostbite, Kashin-Beck disease, and rat bite fever) illustrate the acrophysis principle and in turn their manifestations are explained by that principle.

Lead lines

An 11-month-old female infant was brought in with a 2-day history of vomiting, generalised tonic-clonic seizures, and somnolence. On examination, she was pale, hypotonic, and comatose with a bulging anterior fontanelle. Both pupils were dilated. Cerebrospinal fluid was normal, so we considered lead poisoning as a cause of encephalopathy. Full body radiographs showed dense metaphyseal bands in all the long bones without any flaring or cupping (figure). Haemoglobin was 85 g/L, free erythrocyte protoporphyrin (FEP) was 43 mg/g of haemoglobin, and the blood lead was 297 mg/L. The patient's father made imitation jewellery at home using lead-based paints which were probably the source of lead poisoning. Despite treatment with intravenous edetate disodium calcium, the patient had cardiac arrest and died. The parents were counselled regarding the possibility of lead poisoning in future children.Dense metaphyseal bands or lead lines indicate radioopaque bone at the metaphysis of growing bones and are fairly typical of lead poisoning in young infants with acute encephalopathy. Lead inhibits osteoclastic remodelling, but it has no effect on osteoblasts. Although lead ions are deposited on hydroxyapatite crystal, lead contributes very little to the metaphyseal density, which is due to exuberant calcium deposition in the zone of provisional calcification.Note to potential authorsThe Lancet currently has a large stock of clinical pictures ready for publication. Regretfully, we will not be able to accept any new submissions until January 2004. An 11-month-old female infant was brought in with a 2-day history of vomiting, generalised tonic-clonic seizures, and somnolence. On examination, she was pale, hypotonic, and comatose with a bulging anterior fontanelle. Both pupils were dilated. Cerebrospinal fluid was normal, so we considered lead poisoning as a cause of encephalopathy. Full body radiographs showed dense metaphyseal bands in all the long bones without any flaring or cupping (figure). Haemoglobin was 85 g/L, free erythrocyte protoporphyrin (FEP) was 43 mg/g of haemoglobin, and the blood lead was 297 mg/L. The patient's father made imitation jewellery at home using lead-based paints which were probably the source of lead poisoning. Despite treatment with intravenous edetate disodium calcium, the patient had cardiac arrest and died. The parents were counselled regarding the possibility of lead poisoning in future children. Dense metaphyseal bands or lead lines indicate radioopaque bone at the metaphysis of growing bones and are fairly typical of lead poisoning in young infants with acute encephalopathy. Lead inhibits osteoclastic remodelling, but it has no effect on osteoblasts. Although lead ions are deposited on hydroxyapatite crystal, lead contributes very little to the metaphyseal density, which is due to exuberant calcium deposition in the zone of provisional calcification. Note to potential authors The Lancet currently has a large stock of clinical pictures ready for publication. Regretfully, we will not be able to accept any new submissions until January 2004.

The acrophysis: a unifying concept for enchondral bone growth and its disorders. I. Normal growth.

In order to discuss and illustrate the common effects on normal and abnormal enchondral bone at the physes and at all other growth plates of the developing child, the term "acrophysis" is proposed. Acrophyses include the growth plates of secondary growth centers including carpals and tarsals and apophyses, and the growth plates at the non-physeal ends of small tubular bones. The last layer of development of both physes and acrophysis is the cartilaginous zone of provisional calcification (ZPC). The enchondral bone abutting the ZPC shares similar properties at physes and acrophyses, including the relatively lucent metaphyseal bands of many normal infants at several weeks of age. The bone-in-bone pattern of the normal vertebral bodies and bands of demineralization of the tarsal bones just under the ZPC are the equivalent of those bands. The growth arrest/recovery lines of metaphyses similarly have equivalent lines in growth centers and other acrophyseal sites. Nearly the same effects can also be anticipated from the relatively similar growth plate at the cartilaginous cap of benign exostoses ("paraphysis"). The companion article will explore abnormalities at acrophyseal sites, including metabolic bone disease and dysplasias.

Localization of GABA, GAD65 and GAD67 in Rat Epiphyseal Growth Plate Chondrocytes.

The distribution of γ-aminobutyrate (GABA) and its synthesizing enzyme glutamate decarboxylase (GAD) in the epiphyseal growth plate of the rat long bone was studied by immunohistochemistry. GABA, GAD65 and GAD67 immunoreactive chondrocytes were found in hypertrophic zones of the growth plate, but not in reserve and proliferative zones. In the hypertrophic zone, GABA immunoreactivity was more intense in the maturation zone than in the degenerative zone and the zone of provisional calcification. Patterns of immunoreactivity for GAD65 and GAD67 were almost comparable to those of GABA. In addition, GAD65 and GAD67 mRNAs were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). These results suggest that GABA, which is synthesized de novo in chondrocytes of the growth plate may have certain functional roles in skeletal growth.

Cartilaginous path of physeal fracture-separations: evaluation with MR imaging--an experimental study with histologic correlation in rabbits.

To define the transverse levels of intracartilaginous fractures by using magnetic resonance (MR) imaging and histologic analysis in experimental physeal fracture-separations. Physeal fracture-separations were evaluated with MR imaging in 28 distal femurs and 28 proximal tibias of 22 immature rabbits. The intraphyseal transverse level of injury was graded as juxtaepiphyseal (germinal or proliferative zones) or juxtametaphyseal (hypertrophic zone or zone of provisional calcification). Histologic sections from 23 specimens were studied to assess correlations. We assessed nonenhanced and gadolinium-enhanced T1-weighted, intermediate-weighted, T2-weighted, and spoiled gradient-recalled-echo T1-weighted images. In all MR studies, the injury was visible as a cleft of signal intensity lower than the signal intensity of the physeal cartilage. Juxtaepiphyseal extension, seen in 18 (64%) of 28 fractures, was more frequent in the undulating central part of the distal femoral physis than in the flatter proximal tibial physis (P =.008). In 20 of 23 specimens, MR imaging and histologic findings had excellent correlation for the detection of fracture level and morphology. The course and level of injury within the cartilage in physeal fracture-separations can be defined with MR imaging. Extension into the juxtaepiphyseal physis, a potential risk factor for growth arrest, is detectable with MR imaging; MR imaging and histologic findings correlate well.

Effects of parathyroid hormone‐related peptide on chick growth plate chondrocytes

Parathyroid hormone-related peptide (PTHrP) and parathyroid hormone (PTH) have similar biological effects in vitro that are mediated through the PTH receptor. PTH receptors have been demonstrated in the zone of provisional calcification and the hypertrophic zone of the cartilaginous growth plate. The current study examined the biological effects of PTHrP on chick growth plate chondrocytes. Chondrocytes were exposed to varying doses of PTHrP for 24 h, and the incorporation of radioactive thymidine into DNA was used as an index of proliferation. A dose-dependent stimulation of proliferation was seen, with a maximal 27-fold increase at 50 nM PTHrP. A dose-dependent stimulation of cAMP was seen, with a maximal effect at a dose of 50 nM. Proteoglycan synthesis, measured by incorporation of radioactive sulfate, was stimulated, with a maximal effect of 65% at 1 nM. Collagen synthesis and alkaline phosphatase activity from both cellular and matrix vesicle sources decreased in a dose-dependent fashion, with a maximal inhibition of approximately 50% of the control value. The physiologic significance of the PTH and PTHrP-responsiveness of growth plate chondrocytes is uncertain at the present time. It is possible that PTH or PTHrP, or both, act as a systemic, developmental modulator of cellular proliferation and differentiation in the growth plate.

Sequential Serum Aluminum and Urine Aluminum: Creatinine Ratio and Tissue Aluminum Loading in Infants With Fractures/Rickets

Aluminum toxicity is associated with the development of bone disorders, including fractures, osteopenia, and osteomalacia. Fifty-one infants with a mean (+/- SEM) birth weight of 1007 +/- 34 g, gestational age of 28.5 +/- 0.3 weeks, and serial radiographic documentation at 3, 6, 9, and 12 months for the presence (n = 16) or absence (n = 35) of fractures and/or rickets were studied at the same intervals to determine the serial changes in serum aluminum concentrations and urine aluminum-creatinine ratios. Autopsy bone samples were used to determine the presence of tissue aluminum. Serum aluminum concentrations from 46 infants were stable and similar between groups, with mean values between 15 and 22 micrograms/L. Urine aluminum-creatinine (micrograms per milligram) ratios from 14 infants were higher in infants with fractures and/or rickets (0.26 +/- 0.06 vs 0.12 +/- 0.04) at onset, and rate of decrease in aluminum-creatinine ratio was faster in infants without fractures and/or rickets. All but three infants were tolerating complete enteral feeding at all sampling points. One infant who received aluminum-containing antacid had marked increase in serum aluminum to 83 micrograms/L while urine aluminum-creatinine ratio increased from 0.09 to a peak of 8.53. Vertebrae from three infants at autopsy (full enteral feeding was tolerated for 37 and 41 days in two infants, respectively) showed aluminum deposition in the zone of provisional calcification and along the newly formed trabecula.(ABSTRACT TRUNCATED AT 250 WORDS)