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PubMed1999

Metaphyseal anadysplasia: evidence of genetic heterogeneity.

We report on two unrelated children, a girl and a boy, with regressive metaphyseal dysplasia. Both children had bow legs and a transient growth decline in early childhood. Metaphyseal modifications of the long bones in the children were most conspicuous at an early age and then subsided by age 2 to 3 years. The father of the boy may have had the same disorder, because he was shorter than his sibs and showed mild modifications of the vertebral end plates with mild narrowing of the interpediculate distance of the lumbar spine. The evolution of the metaphyseal dysplasia in the children closely resembled that of metaphyseal anadysplasia (MAD), which is X-linked recessive in inheritance. By contrast, the occurrence of an isolated, affected girl and possible father-to-son transmission reported here were consistent with autosomal dominant transmission, suggesting heterogeneity of MAD. Molecular studies of the type X collagen gene in the boy did not demonstrate any disease-causing mutation.

Adult↗

PubMed2003

Distinctive metaphyseal chondrodysplasia with severe distal radius and ulna involvement (upper extremity mesomelia) and normal height.

Metaphyseal chondrodysplasias (MCD) are skeletal disorders characterized by metaphyseal irregularities and, usually, by short stature. In MCD, wide heterogeneity exists with regard to clinical and radiological changes. We report on a patient with clinical and radiological findings of MCD who had coxa valga and normal height with metaphyseal involvement of the long bones. The short radii and ulnae showed a very severe change in their distal metaphyses, leading to mesomelic shortening confined to the upper limbs. Hematological, ophthalmological, and hearing examinations were normal. This type of MCD appears to represent a yet undescribed syndrome.

Body Height↗

PubMed1991

Rearrangement of the metaphyseal vasculature of the rat growth plate in rickets and rachitic reversal: a model of vascular arrest and angiogenesis renewed.

The morphology of the metaphyseal microvasculature at the epiphysis was examined at both the light and electron microscopic level in rickets and rachitic reversal. The animals studied were normal, rachitic, and rachitic reversed at 8, 24, and 96 hours post-vitamin D administration. The overall architecture of the metaphyseal vessels was significantly altered throughout the intervals examined. In the rachitic animal, arterioles, venules, and capillaries were found adjacent to the growth plate, either directly apposed to the hypertrophic chondrocytes or separated from them by bone-forming cells. These vessels are in many ways similar to the larger arterioles and venules that normally supply the metaphyseal capillary sprouts, but in the normal growing animal are usually located 350-500 microns from the epiphyseal cartilage. The rachitic capillaries appear relatively well differentiated with a partial basement membrane and a perivascular cell lining. In early rachitic reversal, small vascular projections are induced to grow from the large diameter venules that border upon the hypertrophic chondrocytes. These vascular sprouts that invade the epiphyseal cartilage are quite undifferentiated, with no basement membrane or pericyte lining at the sprout apex and occasional abluminal endothelial cell projections. Within 96 hours, the metaphyseal microvasculature has returned to an apparently normal state with only capillaries at the cartilage-vascular interface and larger vessels (arterioles and venules) located several hundred microns deeper into the metaphysis. The sequential processes of differentiation and cessation of capillary growth followed by dedifferentiation and reinitiation of microvascular growth make the rachitic system a unique one in which to study angiogenesis.

Animals↗

PubMed1995

Mutations in three subdomains of the carboxy-terminal region of collagen type X account for most of the Schmid metaphyseal dysplasias.

We have used the polymerase chain reaction and single strand conformation polymorphism (SSCP) methods to analyse the COL10A1 gene, which encodes collagen type X, in DNA samples from patients with metaphyseal dysplasia type Schmid (SMCD) and other related forms of metaphyseal dysplasia. Five cases of SMCD were sporadic and three others were familial. Abnormal SSCP profiles were observed in six instances. In two families, the altered pattern segregated with the phenotype. The heterozygous mutations corresponded to a glycine substitution by glutamic acid at position 595 and to an asparagine substitution by lysine at position 617. In one sporadic case, the sequence studies demonstrated that the individual was heterozygous for a single base deletion (del T 1908) that produced a premature stop codon. Three additional mutations were single base substitutions that affected highly conserved residues at positions 597, 644 and 648. In two additional individuals with SMCD, in two patients with unclassifiable forms of metaphyseal dysplasia, and in one family with epiphyso-metaphyseal dysplasia, SSCP analysis detected neutral polymorphisms in the entire coding sequence of the gene but no mutations. Our results demonstrate that mutations in the carboxy-terminal region of collagen X are specific for the SMCD phenotype. Mutations appear to be clustered into three small subdomains: one of them is rich an aromatic residues, the second includes the putative N-linked oligosaccharide attachment site and the third contains mostly hydrophilic residues. The absence of clinical variability between patients carrying heterozygous single base substitutions or small deletions suggests that, in both instances, the mutant collagen chains either fail to be incorporated into stable trimers or disturb type X collagen assembly.

Base Sequence↗

PubMed1981

Concurrence of metaphyseal fibrous defect and osteosarcoma. Report of a case and review of the literature.

The case of a 15-year-old girl with juxtaposition of a femoral metaphyseal fibrous defect (fibrous cortical defect) and an osteosarcoma is reported. Despite the relatively common occurrence of metaphyseal fibrous defects, their reported association with other bone tumors is exceedingly rare. Only two previous acceptable examples of this association were found. Reports of malignant transformation of metaphyseal fibrous defect were reviewed and rejected because they lacked convincing radiologic or histopathologic evidence of a pre-existent benign fibrous lesion. The finding of a malignant bone tumor in association with a metaphyseal fibrous defect appears to be a chance occurrence.

Adolescent↗

PubMed1989

Fibrous metaphyseal defects. Magnetic resonance imaging appearances.

Sixteen patients with fibrous metaphyseal defects were examined with both plain radiography and magnetic resonance (MR) imaging. Depending on the age of the fibrous metaphyseal defects, characteristic radiomorphologic changes were found which correlated well with MR images. Following intravenous Gadolinium-DTPA injection, fibrous metaphyseal defects invariably exhibited a hyperintense border and signal enhancement. Healed lesions exhibited a transition to normal bone marrow. A line through the maximum longitudinal diameter of a fibrous metaphyseal defect invariably led to a point of tendinous or ligamentous insertion. Coronal MR images demonstrated the maximum longitudinal extension and the respective inserting tendon or ligamentous structure at the epiphyseal line.

Adolescent↗

PubMed1996

Effect of vitamin K2 (menaquinone-7) on bone metabolism in the femoral-metaphyseal tissues of normal and skeletal-unloaded rats: enhancement with zinc.

The effect of vitamin K2 (menaquinone-7) on bone metabolism in the femoral-metaphyseal tissues of normal and skeletal-unloaded rats was investigated. Skeletal unloading was designed using a model of hindlimb suspension; the rats were fed for the 4 days of unloading. The metaphyseal tissues obtained from normal and skeletal-unloaded rats were cultured for 48 h in medium containing either vehicle or vitamin K2 (10(-6) and 10(-5) M). The presence of vitamin K2 (10(-5) M) caused a significant increase in alkaline phosphatase activity and calcium content in the metaphyseal tissues from normal rats. Such an effect was not seen in the bone tissues from skeletal-unloaded rats. Additionally, the presence of zinc sulfate (10(-5) M) in effective concentration produced a significant increase in alkaline phosphatase activity and calcium content in the metaphyseal tissues from normal and skeletal-unloaded rats. In the presence of vitamin K2 (10(-5) M), the stimulatory effect of zinc sulfate on bone calcium content was appreciably enhanced; although this effect was completely abolished by cycloheximide (10(-6) M), an inhibitor of protein synthesis. This study demonstrates that the effect of vitamin K2 (menaquinone-7) on trabecular bone calcification in rats with skeletal unloading-induced osteopenia is enhanced by zinc in vitro. The enhancement with zinc may be based on a newly synthesized protein in the bone tissues.

Alkaline Phosphatase↗

PubMed2005

Quantification of metaphyseal modeling in children treated with bisphosphonates.

There has been recent concern in the literature that the treatment with bisphosphonates in children can have an adverse effect on metaphyseal modeling leading to "drug-induced osteopetrosis". We created a normal database called metaphyseal index in the distal femur so that we could quantify the inwasting modeling process in children on bisphosphonates. Radiographs of the distal femur of 468 normal children who had presented to our institution for orthopedic trauma were examined. A measurement of the distal femoral growth plate width (GPW) was recorded. The femoral width at an interval of 0.5 GPW proximal to the distal femoral growth plate was also recorded (0.5 W). The metaphyseal index was defined as a ratio of 0.5 W/GPW. A graph of the means, one and two standard deviations from the mean, was constructed using the data obtained from this cohort. We found this ratio to be constant with minimal variability regardless of the age or sex of the child. We plotted 20 patients at our institution given bisphosphonates for localized orthopedic complaints. Z scores for girls averaged 0.68 and boys 0.13. Three patients had Z scores >2.0, with values of 2.2, 2.9, and 3.2. Metaphyseal modeling in the distal femur is constant, with slight variation between sexes, resulting in a similar shape of the distal femur throughout childhood. Clinically relevant doses of bisphosphonates given for appropriate indications do not necessarily disturb this process, while the beneficial clinical effect is maintained.

Adolescent↗

PubMed1979

Spondylo-metaphyseal dysplasia (report of a case of common type and three cases of "new varities").

One sporadic case of the common type of spondylo-metaphyseal dysplasia and three cases of "new varieties" are reported. In the author's opinion spondylo-metaphyseal dysplasias are much more common than generally recognised. Brachyolmie represents spondylo-metaphyseal dysplasia with mild-minimal metaphyseal changes.

Arm↗

PubMedDate not supplied

Capital necrosis, metaphyseal cyst and subluxation in coxa plana.

Three specific elements associated with a poor prognosis in Legg-Calvé-Perthes disease, i.e., capital necrosis, metaphyseal cyst and subluxation, have been selected for study to determine the effect of each on the end result. A retrospective analysis was made of 337 children who received non-weight-bearing treatment. Half of the patients were treated in abduction splints, over a third with bed rest and traction and the remainder with a variety of routines including sling and crutches, wheelchair or bed rest alone. The group was treated as representing a common pool of therapy and was analyzed statistically in this overall manner. End results were graded by the Knud Mose method (concentric circle matching plus epiphyseal quotient determinations). Good and fair results were combined into an acceptable category while the poor results were considered unacceptable. Femoral capital necrosis was present either segmentally or totally. A classification was devised of three grades of partial epiphyseal involvement and one of total necrosis. The patients with total necorsis (Group IV) had a higher percentage of poor results than those with segmental involvement (Groups I, II and III). The lowest percentage of poor results correlated with the least involvement of the femoral head (Group III). Total head involvement occurred in the unacceptable group one and one half times as frequently as it did in the acceptable group. Metaphyseal cyst formation exhibited a close relationship to the fragmentation of the capital epiphysis. It is suggested that the metaphyseal lesion itself is part of the overall necrotic process and that the "cyst" is resorption associated with revascularization as healing is taking place. We noted twice the frequency of metaphyseal cysts in patients with poor results in comparison to that found in the acceptable group. Subluxation is defined as loss of acetabular centration of the femoral head due to upward and outward displacement. Increased distance between the medial margin of the metaphysis and the lateral limb of the "tear drop" figure is practically a universal finding on early roentgenograms and was not considered "subluxation" in this prognostic evluation. In the series under study there were three times as many subluxations in the poor result group as in the group with acceptable results. A prognostic profile revealing three of the above-listed features was associated with a poor result and should constitute an objective basis of evaluation of new forms of therapy.

Bone Cysts↗

PubMed2002

The use of BoneSource hydroxyapatite cement for traumatic metaphyseal bone void filling.

OBJECTIVE: This prospective, randomized study was performed to determine whether a new, in situ setting hydroxyapatite cement is as safe or effective as autologous cancellous bone graft for the treatment of metaphyseal bone voids secondary to trauma. This was a multicenter study including Level I trauma centers and university hospitals. Thirty-eight patients who sustained an acute closed or open type I fracture of the humerus, radius, ulna, femur, tibia, or calcaneus and had a traumatic bone void requiring grafting of the metaphyseal or cancellous bone area were enrolled. Open reduction and internal fixation of the fracture was performed with use of either autologous cancellous bone or BoneSource hydroxyapatite cement to fill traumatic metaphyseal voids. Main outcome measures included maintenance of reduction, fracture healing, pain at defect site, pain at donor site, and clinical function of the limb. RESULTS: Patients treated with BoneSource had an 83% success rate in maintaining reduction, whereas patients treated with autograft had a 67% success rate. A successful clinical outcome, as measured by a healed fracture with minimal to no pain, moderate to maximum function, and no or minor donor site complications, was seen in 69% of patients treated with BoneSource and 57% of patients treated with autograft. In patients with at least 1 year of follow-up, the overall success rate was 79% in the BoneSource group and 70% in the autograft group. CONCLUSION: BoneSource is safe and effective when used to fill traumatic metaphyseal bone voids. It is at least as good as autograft for treatment of these defects.

Adolescent↗

PubMed1992

Limb deformity and metaphyseal abnormalities in thalassaemia major.

Regular bone survey radiographs have allowed identification of limb deformity and metaphyseal changes in several patients with thalassaemia major treated at the Adelaide Children's Hospital. Following the progression of limb deformity in five of these patients who were receiving human growth hormone therapy, the records of 25 thalassaemia patients were reviewed. Six patients had evidence of limb deformity, four of whom also had metaphyseal changes. Three additional patients had metaphyseal changes alone. Patients with either type of skeletal change shared similar characteristics, including younger age, earlier commencement of desferrioxamine therapy, better compliance and, in general, lower levels of ferritin. Females predominated in both groups. The frequency of sensorineural hearing loss was similar in affected and nonaffected groups and biochemical parameters, especially plasma calcium, phosphate, alkaline phosphatase, and zinc, which were normal in all patients. The cause of these skeletal changes is not clear; however, several potential factors need to be considered. Among these are focal marrow expansion in the metaphyseal region due to incomplete suppression of erythropoiesis and possible effects of desferrioxamine, including direct interference with bone growth, altered response of bone to inflammation or infection, and altered bone metabolism related to chelation of trace metals. While we can only speculate on aetiological factors, it is clear that human growth hormone therapy has resulted in exaggeration of deformity due to an increased rate of bone growth or decreased rate of mineralization of physeal cartilage. We believe that bone survey radiographs are useful in early identification of skeletal changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1981

Histochemistry and ultrastructure of the growth plate in metaphyseal dysostosis: further observations on the structure of the cartilage matrix.

The metaphyseal dysostosis growth plate matrix was examined by alcian blue-magnesium chloride histochemistry and electron microscopy. The metaphyseal dysostosis matrix is uniformly alcian blue positive at all molarities of MgCl2 up to 1.0 M. In normal growth plates, the vertical septa become alcian blue negative at 0.5 to 0.6 M MgCl2. At 1.0 MgCl2, metaphyseal dysostosis plates are weakly periodic acid-Schiff (PAS) positive compared to intense PAS reactions in normal growth plates. The histochemical findings correlate well with the decreased collagen content of the matrix as seen by electron microscopy, resulting in a relative increase in proteoglycan granules. The findings indicate that the previously described cellular defect seen in metaphyseal dysostosis chondrocytes is related to an abnormal cartilage matrix that mineralizes poorly and is not easily degraded.

Adolescent↗

PubMed1993

Cranio-metaphyseal dysplasia.

Cranio-metaphyseal dysplasia in two brothers, aged fourteen and twelve, is reported. Both brothers presented with deafness, repeated episodes of cold and cough and mouth breathing. Striking craniofacial configuration consisted of hypertelorism, prominent glabella and zygomatic arches, mandibular prognathism and overgrowth of middle third of face. Both patients had genu valgum deformity. Low intelligence and poor scholastic performance present in both brothers were attributed to deafness. Radiographic features consisted of obtuse mandibular angle, defective dentition, sclerotic frontal sinuses, sclerotic mastoids and temporal bones. Splaying of metaphyses of long bones was associated with mild sclerosis. Mild degree of widening of ribs was also present. One brother also had hallux valgus deformity. The radiographic and clinical differentiation of cranio-metaphyseal dysplasia and metaphyseal dysplasia (Pyle's disease) is highlighted.

Adolescent↗

PubMed2005

Changes in mineralization and biomechanics of tibial metaphyses in splinted rats.

The effect of 3 wk of splintage of a single hindlimb on the midarea and mineral content of both tibial metaphyses was assessed immediately after splint removal and after 1 mo of mobilization in 12-wk-old Sprague-Dawley rats. Immobilization reduced tibial metaphyseal bone mineral density (BMD) in immobilized limbs compared with "free" limbs of splinted animals and with controls. These changes persisted and were accentuated by relatively greater increases in tibial metaphyseal BMDs of unsplinted (control) animals after 7 wk. Immediately after splintage, tibial metaphyseal areas and total mineral contents of both hindlimbs of splinted animals were reduced compared with those of unsplinted animals. However, the relationship between mineralization and area differed between the free and immobilized limbs of splinted animals. The breaking strain and the breaking energy of immobilized and free femurs of splinted animals were impaired 4 wk after the removal of the splint. This impairment was correlated with an effect of splintage on femoral size with some additional local effect from immobilization. Thus osteoporotic changes consequent on immobilization include both local effects on mineralization and general effects on growth, which may separately influence the elastic properties of bone.

Adaptation, Physiological↗

PubMed2004

Partial epiphyseal preservation and intercalary allograft reconstruction in high-grade metaphyseal osteosarcoma of the knee.

BACKGROUND: The purpose of this study was to analyze a series of patients with a high-grade metaphyseal osteosarcoma of the knee who had been treated with a transepiphyseal resection, with preservation of the distal femoral and the proximal tibial (articular) portions of the epiphysis, and an intercalary allograft reconstruction. METHODS: The cases of thirteen patients with a high-grade metaphyseal osteosarcoma around the knee who had transepiphyseal resection and reconstruction with an intercalary allograft were retrospectively reviewed at a mean of sixty-three months. Complications, disease-free survival of the patient, final preservation of the limb and epiphysis, and functional results according to the Musculoskeletal Tumor Society scoring system were documented at the time of the latest follow-up. RESULTS: At the final follow-up examination, eleven of the thirteen patients continued to be disease-free. One patient died of bone and pulmonary metastases with no evidence of local recurrence, and the remaining patient had no evidence of disease after resection of a local recurrence of the tumor in the soft tissues. No patient had a local recurrence in the remaining epiphysis. Seven patients had complications that included a fracture (three patients), diaphyseal nonunion (two), deep infection (one), and a local recurrence in the soft tissues (one). The allograft was removed in only four of these patients. At the latest follow-up examination, twelve patients were alive with preserved limbs. In one patient, the epiphysis, which originally had been preserved, was resected because of a metaphyseal fracture, and the limb was reconstructed with an osteoarticular allograft. The patients with a preserved epiphysis had an average functional score of 27 points (maximum, 30 points). CONCLUSIONS: Preservation of the epiphysis in high-grade metaphyseal osteosarcoma at the knee is an alternative in carefully selected patients. Crucial factors needed to obtain local tumor control and achieve an acceptable functional result are a positive response to chemotherapy, accurate preoperative assessment of tumor extension to the epiphysis, and appropriate fixation techniques for intercalary allografts. LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series [no, or historical, control group]). See Instructions to Authors for a complete description of levels of evidence.

Adolescent↗

PubMed2005

Partial epiphyseal preservation and intercalary allograft reconstruction in high-grade metaphyseal osteosarcoma of the knee.

Antineoplastic Agents↗

PubMed1997

Normal gadolinium-enhanced MR images of the developing appendicular skeleton: Part 2. Epiphyseal and metaphyseal marrow.

OBJECTIVE: We have studied how gadolinium enhancement of T1-weighted MR images affects the expected normal differences in signal intensity between metaphyseal hematopoietic and epiphyseal fatty marrow. We have also analyzed how enhancement affects the expected normal changes in the MR images of the marrow due to fatty conversion. MATERIALS AND METHODS: We analyzed gadolinium-enhanced MR images of normal distal femurs in 18 immature rabbits that were 5-11 weeks old and of normal proximal femurs in 18 infants, children, and young adults who were 2 months to 21 years old. In all subjects, we studied the change with age in signal intensity and enhancement ratio of the epiphyseal and metaphyseal marrow. In the rabbits, marrow composition and transformation were histologically verified. RESULTS: On unenhanced T1-weighted MR images of the rabbits and of the infants, children, and young adults, epiphyseal signal intensity always exceeded metaphyseal signal intensity; however, the enhancement ratio was always greater in the metaphysis. The signal intensity in metaphyseal and epiphyseal marrow on unenhanced MR images increased with age. However, enhancement ratios decreased with age in both areas. In the rabbits, histologic studies showed more fatty marrow in the epiphysis than in the corresponding metaphysis and an age-related increase in marrow fat at both sites. CONCLUSION: In the marrow of the extremities, gadolinium enhancement is greater in the (hematopoietic) metaphysis than in the (fatty) epiphysis. In both areas, enhancement decreases as the marrow becomes more fatty. On T1-weighted images, administration of a gadolinium-containing contrast agent reduces the normal contrast between hematopoietic and fatty marrow and obscures the changes in marrow signal intensity due to fatty conversion.

Adolescent↗