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Growth slowdown and arrest lines.

Transversely oriented lines within the metaphyses and proximate diaphyses were studied in multiple specimens from cadavers and amputation specimens from skeletally immature individuals. These lines, evident as transverse trabecular bands of increased radiodensity, proved histologically to be thickened, transversely interconnected trabecular networks, with more typical, longitudinally oriented trabecular bone on either side. They appeared following a temporary slowdown or cessation of rapid longitudinal bone formation in the primary spongiosa and were parallel to the contours of the contiguous physis. When growth rates were normal, longitudinally oriented trabeculae with interspersed marrow elements predominated at the zone of transformation of cartilage to bone. However, when growth rates slowed down or were temporarily arrested, the trabeculae thickened and fused with each other transversely. When the abnormal process (e.g., fracture or systemic illness) responsible for growth retardation subsided, more rapid rates of endochondral growth and transformation resumed, forming the more characteristic normal longitudinal trabecular orientation. As the bone elongated, these transverse lines were progressively displaced from the physis. As the metaphyseal bone was remodeled to diaphyseal bone, these trabecular lines were gradually remodeled and usually disappeared completely by the time skeletal maturity was reached.

Adolescent↗

Late skeletal deformities following meningococcal sepsis and disseminated intravascular coagulation.

Late skeletal deformities following meningococcemia associated with disseminated intravascular coagulation are rare. Two basic lesions have been described: epiphyseal avascular necrosis and epiphyseal-metaphyseal defects. These occur primarily in the lower extremities and result in angular deformity and leg length inequality. We recently encountered these lesions in a child 3 years following sepsis. The etiology appears to be acute vascular thrombosis of epiphyseal and metaphyseal vessels mediated through the generalized Shwartzman reaction. An increased incidence of these deformities may be anticipated as more children survive fulminant meningococcemia.

Bone Diseases, Developmental↗

Arthroscopic visualization during excision of a central physeal bar.

A centrally located developmental physeal bar in the proximal tibia was removed via a metaphyseal window. The use of an arthroscope to assist in the complete removal of the bone bridge is described. The arthroscope improved visualization and allowed reduction in the size of the metaphyseal window. At 2-year follow-up, the growth plate showed no evidence of bar reformation.

Arthroscopy↗

Effects of physeal distraction on the vascular supply of the growth area: a microangiographical study in rabbits.

To study the effects of physeal distraction on growth plate vascularity, microangiography was performed in 45 growing rabbits. Marked enlargement of the epiphyseal arteries and defective metaphyseal capillary filling were observed in association with hyperplasia and separation of the physes after 3 days of distraction, and the changes still persisted locally in specimens distracted for 21 days. New capillaries were observed in the hyperplastic physes and in separation gaps at 21 days. Vascular anastomoses across the physes were noted after 6 weeks of follow-up. Epiphyseal capillary enlargement may indicate increased nutritional demands of the physis, whereas metaphyseal changes are probably related to separation in the hypertrophic chondrocyte zone.

Animals↗

A case of Satoyoshi's syndrome.

Satoyoshi's syndrome is a rare neurologic disorder characterized by progressive muscle spasms, alopecia, diarrhea, and skeletal abnormalities. We describe a 21-year-old woman with Satoyoshi's syndrome whose skeletal changes were followed for 15 years until after she had reached skeletal maturity. The patient developed slipping of the epiphyses in the proximal humeri and femurs and metaphyseal lesions mimicking metaphyseal chondrodysplasia. These lesions were a consequence of physeal injuries caused by the recurrent muscle spasms.

Alopecia↗

A critique of the concept of quality of life.

Taking a philosophical approach, ancient Greek philosophers and Christians began to investigate the concept of quality of life. Later, such philisophical pursuit was replaced by the school of positivism, which indicated that science was and still is the only valid form of enquiry. Through such positivistic science, the metaphysical nature of the concept of quality of life is thought to be uncovered. However, the later Wittgensteinian philosophical thoughts demonstrated that there is no metaphysical understanding of any concepts but there is only knowledge of playing language games. In the light of this philosophy, prior to any scientific investigations, researchers have already understood and agreed on the concept of quality of life by playing language games. From the above philosophical analyses, outlines some implications for health care research.

Health Services Research↗

Coincidence, historical repetition, and self-knowledge: Jung, Vico, and Joyce.

Jung develops synchronicity as an a causal principle of connection by recounting various examples of meaningful coincidence from experience and by analysing various systems of divination, notably the I Ching. Philosophical theory of causality has given no significant attention to synchronicity; the events of synchronicity are regarded as chance. The Neapolitan philosopher Giambattista Vico (1668-1744) developed a doctrine of historical experience and of self-knowledge that grounds the phenomenon of synchronicity in a metaphysics. James Joyce employed Vico's conception of language and historical cycles as the basis of Joyce's final literary work, Finnegans Wake. Vico's metaphysical sense of synchronicity and Joyce's literary formulation offer a grounding of this principle in non-divinatory sources in modern Western thought, something which Jung's discussion does not provide. These philosophical and literary perspectives complement Jung's to offer an expanded context in which to recognize synchronicity and to make sense of it.

Humans↗

Skeletal phenotype in patients with Shwachman-Diamond syndrome and mutations in SBDS.

Pancreatic exocrine and bone marrow dysfunctions are considered to be universal features of Shwachman-Diamond syndrome (SDS) whereas the associated skeletal dysplasia is variable and not consistently observed. The genetic defect in SDS has recently been identified; causative mutations have been shown in the SBDS gene. The aims of this study were to characterize the nature, frequency, and age-related changes of radiographic skeletal abnormalities in patients with SBDS mutations and to assess genotype-phenotype correlation. Fifteen patients (mean age 9.7 years) with a clinical diagnosis of SDS and documented SBDS gene mutations were included. Review of their skeletal radiographs showed abnormalities in all patients. The skeletal changes were variable, even in patients with identical genotypes. The typical features were (1) delayed appearance of secondary ossification centers, (2) variable widening and irregularity of the metaphyses in early childhood, followed by progressive thickening and irregularity of the growth plates, and (3) generalized osteopenia. There was a tendency towards normalization of the epiphyseal maturation defect and progression of the metaphyseal changes with age. The results suggest that the characteristic skeletal changes are present in all patients with SDS and SBDS mutations, but their severity and localization varies with age. No phenotype-genotype correlation was observed.

Adolescent↗

Dominantly inherited craniodiaphyseal dysplasia: a new craniotubular dysplasia.

We describe a mother and her male infant affected with a craniotubular dysplasia characterized by severe craniofacial hyperostosis and sclerosis with obliteration of paranasal sinuses and foramina of the skull base. Subsequent severe bilateral hearing loss and facial diplegia with relative sparing of the optic nerves were noted. The long bones show extreme asymmetric hyperostosis and sclerosis of the diaphyses and evidence of a modelling defect in the metaphyses. The spine, ribs, clavicles, and pelvis all show some degree of sclerosis and defective modelling, but are less severely involved. According to the definition by Gorlin, this disorder would best be classified as craniodiaphyseal dysplasia. Distinguishing features in these two patients as contrasted to previously described cases include a greater degree of hyperostosis and sclerosis than that described for other patients with craniodiaphyseal dysplasia, apparent dominant transmission, and significant metaphyseal involvement.

Adult↗

Microcephalic osteodysplastic dwarfism (type II-like) in siblings.

We report about two sibs showing a common pattern of birth defects, with a pedigree suggestive of autosomal recessive heredity. The main features are intrauterine growth failure with very low birthweight; disproportionate dwarfism with predominantly distal shortening of limbs; small cubitally inclined clenched hands; microcephaly with Seckel-like facies and delayed psychomotor development. X-ray findings include metaphyseal flare, V-shaped femoral metaphyses and bowing of forearms. Primordial microcephalic osteodysplastic dwarfism Type II is discussed. Metabolic and nutritional data are presented and discussed.

Diseases in Twins↗

Development of sensory innervation in rat tibia: co-localization of CGRP and substance P with growth-associated protein 43 (GAP-43).

The development of sensory innervation in long bones was investigated in rat tibia in fetuses on gestational days (GD) 16-21 and in neonates and juvenile individuals on postnatal days (PD) 1-28. A double immunostaining method was applied to study the co-localization of the neuronal growth marker growth-associated protein 43 (GAP-43) and the pan-neuronal marker protein gene product 9.5 (PGP 9.5) as well as that of two sensory fibre-associated neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP). The earliest, not yet chemically coded, nerve fibres were observed on GD17 in the perichondrium of the proximal epiphysis. Further development of the innervation was characterized by the successive appearance of nerve fibres in the perichondrium/periosteum of the shaft (GD19), the bone marrow cavity and intercondylar eminence (GD21), the metaphyses (PD1), the cartilage canals penetrating into the epiphyses (PD7), and finally in the secondary ossification centres (PD10) and epiphyseal bone marrow (PD14). Maturation of the fibres, manifested by their immunoreactivity for CGRP and SP, was visible on GD21 in the epiphyseal perichondrium, the periosteum of the shaft and the bone marrow, on PD1 in the intercondylar eminence and the metaphyses, on PD7 in the cartilage canals, on PD10 in the secondary ossification centres and on PD14 in the epiphyseal bone marrow. The temporal and topographic pattern of nerve fibre appearance corresponds with the development of regions characterized by active mineralization and bone remodelling, suggesting a possible involvement of the sensory innervation in these processes.

Animals↗

Cortical bone development under the growth plate is regulated by mechanical load transfer.

Longitudinal growth of long bones takes place at the growth plates. The growth plate produces new bone trabeculae, which are later resorbed or merged into the cortical shell. This process implies transition of trabecular metaphyseal sections into diaphyseal sections. We hypothesize that the development of cortical bone is governed by mechanical stimuli. We also hypothesize that trabecular and cortical bone share the same regulatory mechanisms for adaptation to mechanical loads. To test these hypotheses, we monitored the development of the tibial cortex in growing pigs, using micro-computer tomography and histology. We then tested the concept that regulatory mechanisms for trabecular bone adaptation can also explain cortical bone development using our mechanical stimulation theory, which could explain trabecular bone (re)modelling. The main results showed that, from the growth plate towards the diaphysis, the pores of the trabecular structure were gradually filled in with bone, which resulted in increased density and cortical bone. The computer model largely predicted this morphological development. We conclude that merging of metaphyseal trabeculae into cortex is likely to be governed by mechanical stimuli. Furthermore, cortex development of growing long bones can be explained as a form of trabecular bone adaptation, without the need for different regulatory mechanisms for cortical and trabecular bone.

Adaptation, Physiological↗

Chondromodulin-I expression in the growth plate of young uremic rats.

BACKGROUND: Growth retardation of chronic renal failure is associated with alterations in the growth plate suggestive of a disturbed chondrocyte maturation process and abnormal vascular invasion at the chondro-osseous interphase. Chondromodulin I (ChM-I) is a potent cartilage-specific angiostatic factor. Its pattern of expression in the uremic rat growth plate is unknown. Persistence of ChM-I synthesis and/or imbalance between ChM-I and vascular endothelial growth factor (VEGF) expressions might play a role in the alterations of uremic growth plate. METHODS: Growth cartilage ChM-I expression was investigated by immunohistochemistry, in situ hybridization, and reverse transcription-polymerase chain reaction (RT-PCR) in growth-retarded young uremic rats (UREM), control rats, fed ad libitum (SAL) or pair-fed with the UREM group (SPF), and uremic rats treated with growth hormone (UREM-GH). VEGF expression was analyzed by immunohistochemistry. RESULTS: ChM-I and ChM-I mRNA were confined to the proliferative and early hypertrophic zones of growth cartilage. A similar number of chondrocytes per column was positive for ChM-I in the 4 groups. In accordance with the elongation of the hypertrophic stratum in uremia, the distance (X+/-SEM, microm) between the extracellular ChM-I signal and the metaphyseal end of growth cartilage was higher (P < 0.003) in UREM (236 +/- 40) and UREM-GH (297 +/- 17) than in SAL (92 +/- 7) and SPF (113 +/- 6). No differences in ChM-I expression were appreciated by RT-PCR. Similar VEGF positivity was observed in the hypertrophic chondrocytes of all groups. CONCLUSION: In experimental uremia, expansion of growth cartilage does not result from increased or persistent expression of ChM-I or from reduced VEGF expression at the cartilage-metaphyseal bone interphase. GH treatment does not modify ChM-I and VEGF expressions.

Animal Nutritional Physiological Phenomena↗

The intraosseous blood supply of the canine radius: implications for healing of distal fractures in small dogs.

The intraosseous vascular anatomy of the radius was studied in 12 pairs of canine cadaver limbs. Six pairs of specimens were obtained from small-breed dogs (less than 6 kg) and six pairs were obtained from large-breed dogs (18 to 30 kg). All specimens were studied after arterial injection with India ink. Samples were fixed, frozen, then sectioned and processed using a modified Spalteholz technique. In all specimens, the intraosseous blood supply arose from the nutrient artery with its associated branches and the metaphyseal arteries. In small-breed dogs, there was decreased vascular density at the distal diaphyseal-metaphyseal junction compared with large-breed dogs. The reduced vascularity corresponded to the region associated with a poor prognosis for fracture healing in small-breed dogs. This regional association suggests that a decreased vascular supply in the distal radius may contribute to a higher frequency of delayed union and nonunion in smaller dogs.

Animals↗

Biomechanical comparison of the trocar tip point and the hollow ground tip point for smooth external skeletal fixation pins.

OBJECTIVE: To compare the insertional characteristics of external fixator pins with hollow ground (HG), modified HG, and trocar (T) points. STUDY DESIGN: An acute, in vitro biomechanical evaluation. SAMPLE POPULATION: Thirteen radii from canine cadavers. METHODS: A total of 16 T-tipped and 16 HG-tipped pins were inserted into 8 canine radii. Ten pins of each modification of the HG tip (length of the cutting edge reduced by 0.127 mm and 0.254 mm, respectively) were inserted into another five radii. All pins were inserted with low-speed power drilling and 80 N drilling load. Differences between peak tip temperature, drilling energy, and pullout force were determined for each pin type at both diaphyseal and metaphyseal locations. RESULTS: HG-tipped pins showed a 40% lower tip temperature in diaphyseal bone, a 25% reduction in drilling energy in diaphyseal bone, and a reduction of pullout force in both diaphyseal (65%) and metaphyseal (50%) bone compared with T-tipped pins. HG 0.254-mm pins generated higher tip temperatures and had greater pullout than HG pins in diaphyseal bone. CONCLUSIONS: The HG tip was a more efficient design; however, the reduction in pullout force suggests that, because a better hole was drilled, radial preload is reduced. Reduction of the cutting edge by 0.254 mm increased the pullout force but also increased the temperatures. CLINICAL RELEVANCE: Thermal and microstructural damage are reduced by the HG tip, but pin-bone interface stability is also compromised. The use of a tip with 0.254 mm reduction in the cutting edge may optimize the biological and mechanical factors at the pin-bone interface.

Animals↗

Mechanical performance of a screw-type veterinary suture anchor subjected to single load to failure and cyclic loads.

OBJECTIVE: To characterize the mechanical performance of a veterinary bone anchor under static and cyclic loads. STUDY DESIGN: Mechanical testing study. ANIMALS: Cadaveric canine humeri. METHODS: Humeri (6 pairs) were collected from skeletally mature dogs (mean [+/-SD] age, 17.2+/-2.1 months; weight, 20.8+/-1.5 kg). Bone anchors were inserted in the proximal metaphysis using nylon, and were longitudinally extracted. For the opposite humerus, anchors were subjected to longitudinal cyclic load (50% of the load at failure of their pair) for 1200 cycles then longitudinally loaded to failure. Anchors were then installed in a similar and adjacent area of these 2(nd) humeri with nylon and cyclically tested perpendicular to the axis of anchor insertion (100% of the longitudinal holding power of their pair) for 1200 cycles, then perpendicularly loaded to failure. Paired t-tests were used to compare holding power before and after longitudinal cyclic testing. RESULTS: Longitudinal holding power of the screw-type anchor in the proximal humerus was 385+/-30 N. Anchor pullout was the only mode of failure. Anchors in the paired humeri did not fail after 1200 cycles of 50% longitudinal loading, and post-cycle holding strength was not different (335+/-87 N; P=.32). Perpendicularly loaded anchors did not fail after 1200 cycles of 100% of opposite longitudinal holding strength, and had post-cycle perpendicular holding strengths of 514+/-72 N. Suture breakage was the mode of failure. CLINICAL RELEVANCE: Bone anchor holding strength is dependent on orientation of suture load. Screw-type bone anchor holding strength was not affected by longitudinal cyclic loading, and holding strengths of approximately 385 N can be expected in metaphyseal bone of large-breed mature dogs. Perpendicularly loaded anchors have higher failure loads, and holding strength of approximately 514 N can be expected in metaphyseal bone of the proximal humerus.

Animals↗

Congenital rickets. Study of the evolution of secondary hyperparathyroidism.

A case of congenital rickets of nutritional origin is described in a light-for-date premature infant (gestational age 34 weeks, birthweight 1 100 g). X-rays of the long bones showed spread, frayed and cupped metaphyses at birth and at the age of 16 days. Serum calcium was 8.2 mg/100 ml, phosphorus 3.4 mg/100 ml and alkaline phosphatase (A.P):323 IU/ml (N less than or equal to 200) at the age of 3 days. Very high level of serum immunoreactive parathroid hormone (iPTH) was found at the age of 16 days=295 micronlEq/ml (N less than or equal to 50). Evidence of maternal vitamin D deficiency was demostrated by low plasma 25-hydroxycholecalciferol (25-OH-CC):1.0 ng/ml (N:13.2+/-4.2) soon after delivery; it was found to be normal (10.2 ng/ml) six months later. Ca infusion (15 mg/kg/3 h) resulted in a marked fall of serum iPTH (280 to 84 micronlEq/ml). Administration of vitamin D2 (2400 IU/day for 10 days) induced some healing of the metaphyses; A. P. remained elevated (400 IU/ml); plasma 25-OH-CC was normal 10.2 ng/ml and serum iPTH was 115 micronlEq/ml. When 25-OH-CC was given orally for ten days (15 microng/day), plasma 25-OH-CC rose to 64.5 ng/ml with a minor change of serum iPTH (94 micronlEq/ml); X-rays of the bones showed osteoporosis. These results suggest a reduced convertion of 25-OH-CC into 1-25-(OH)2-CC.

Adult↗

Bone infection in the bovine appendicular skeleton: a clinical, radiographic, and experimental study.

Four hundred and forty-five bovines with bone infection of the appendicular skeleton were selected for clinical and radiographic assessment. A distinction was made between hematogenous and post-traumatic origin (wound/fracture). Bone infection was classified into four types according to the site of infection: type 1 is metaphyseal and/or epiphyseal osteomyelitis close to the growth plate; type 2 is primary subchondral osteomyelitis mostly accompanied by septic arthritis; type 3 is infectious osteoarthritis with subchondral osteomyelitis implicating that infection in the subchondral bone originates from the infection. Type 4 summarizes bone infections which can not be categorized in the previous groups. Hematogenous osteomyelitis is 3.2 times more frequent than post-traumatic osteomyelitis. Within the different groups, the relation of hematogenous to post-traumatic infection changed significantly. In type 1 infection the ratio was 5/1, in type 2 the ratio was 8/1 and in type 3 it was 3/1. Epiphyseal or metaphyseal osteomyelitis exhibited early radiographic bone changes, whereas with infection eminating from the joint, the bone lesions were detected later, because the bone was infected as a consequence of a primary septic arthritis. In smaller bones, severe and complete bone destruction was often present. Hematogenous bone infection never involved the entire diaphysis. Actinomyces pyogenes was discovered to be the main etiologic agent, whether or not combined with anaerobes. Bone fragments from the metaphysis of young calves were subjected to the effect of pure cultures of different bacteria. Radiographic changes to the structure of the bone were not identified within 2 weeks. Rapid radiographic changes in osteomyelitis cannot be explained by the direct effect of the bacteria on bone tissue in vivo. General infections of the lungs, disorders of the intestines and other internal organs were rarely responsible for osteomyelitis or septic arthritis. Osteomyelitis and infectious osteoarthritis is probably often induced by external and internal traumatic events to joints and bones in cattle.

Actinomycosis↗