Biomedical subjects

Michael Amling

Publications and source records attributed to Michael Amling.

25 records · Page 2Linked to original sources

PubMed2004

Resorbability of bone substitute biomaterials by human osteoclasts.

Third generation biomaterials are being designed with the aim that once implanted they will help the body to heal itself. One desirable characteristic of these materials in bone is their ability to be remodeled, i.e. that osteoclasts resorb the material and it is subsequently replaced by newly formed bone through osteoblastic activity. So far the only way to test this biological property of bone substitutes are animal experiments with all their limitations like ethics, costs and limited transferability to man. The present study was designed, to develop a human in vitro assay, allowing to generate human osteoclasts directly on the biomaterial. The assay was validated using calcium phosphate cement and PMMA as biomaterials. Quantification was performed by raster electron microscopy and computer assisted image analysis. Dentin was used as internal standard. Our assay shows iso-bone resorbability of calcium phosphate cement in comparison to unresorbable PMMA cement. Both current clinical orthopedic practice and future skeletal engineering may profit from the availability and use of a test system for the assessment of resorption quality. The assay presented here allows to address this question of resorbability and to select the best materials for the use as bone substitutes in specific patients.

Absorbable Implants↗

PubMed2004

Absence of mouse pleiotrophin does not affect bone formation in vivo.

Pleiotrophin (Ptn) is an extracellular matrix protein that regulates hippocampal synaptic plasticity and learning behavior in vivo. Since the overexpression of Ptn in transgenic mice leads to increased bone formation, we analyzed whether a deficiency in Ptn expression would have a negative effect on bone remodeling. Bones from Ptn-deficient mice and wild-type littermates were analyzed using radiography, muCT imaging and undecalcified histology. Biomechanical stability was determined in a three-point-bending assay. Cellular activities were assessed using dynamic histomorphometry and the determination of urinary collagen degradation products. Skeletons of Ptn-deficient mice have no gross abnormalities, displayed a normal size, and showed no differences in growth plate organization compared to wild-type littermates. There were no obvious differences in bone mass as determined by radiographic and muCT imaging. The absence of a bone remodeling phenotype in Ptn-deficient mice was further confirmed using static histomorphometry and biomechanical testing. Finally, the number, morphology, and function of osteoclasts, osteoblasts, and osteocytes were not altered in Ptn-deficient mice compared to wild-type littermates. The complete skeletal analysis of Ptn-deficient mice presented here demonstrates that the lack of Ptn in mice does not affect bone formation in vivo. Therefore, Ptn does not play a significant role in normal bone physiology.

Animals↗

PubMed2004

Clinical relevance of calcaneal bone cysts: a study of 50 cysts in 47 patients.

The clinical relevance and nature of calcaneal cysts is controversial. The risk of pathologic fracture is undefined and diagnostic criteria to differentiate between cysts in patients who can be treated nonoperatively and patients who require surgical intervention are not available. To address these questions, 50 calcaneal bone cysts in 47 patients were evaluated. The majority of cysts (40 of 50) were asymptomatic and were treated nonoperatively. Cysts reaching a critical size, defined as 100% intracalcaneal cross section in the coronary plane and at least 30% in the sagittal plane, are at risk for becoming symptomatic and at risk for fracture. Fracture is a significant complication and occurred in four of 47 patients, three of whom were treated by open reduction internal fixation and bone grafting. In addition, six patients with symptomatic critical size cysts without apparent fracture were treated by curettage and subsequent autogenous bone grafting or calcium-phosphate cement filling, and there were no recurrences. We report one of the largest series of cysts in the calcaneus. The results suggest that calcaneal cysts are clinically relevant because of the potential risk of fracture and that size is a significant factor in terms of the treatment of the cyst.

Adolescent↗

PubMed2003

Aneurysmal bone cysts of the sacrum. Clinical report and review of the literature.

BACKGROUND: Aneurysmal bone cysts, first described by Jaffe and Lichtenstein in 1942, are benign lesions that may easily be mistaken for a malignant tumor both radiographically and pathologically. These diagnostic problems are due to their rapid growth, extensive destruction of bone, wide extraosseous tumor masses, and marked cellular exuberance. The differential diagnosis of aneurysmal bone cysts including giant cell tumor, calcified solitary bone cysts, low-grade osteosarcoma, and teleangiectatic osteosarcoma becomes even more complicated when the lesion arises at sites other than the long bones and presents with extensive extraosseous, soft-tissue tumor masses. The latter cases--especially when they occur as sacral or presacral tumors--present challenges with respect to successful treatment, which should combine surgical removal of the entire lesion following oncological criteria to prevent recurrences and osteosynthesis to guarantee the biomechanical stability of the spinal-pelvic junction. Here we report on the clinical case of a female patient with an aneurysmal bone cyst of the sacrum and extensive extraosseous tumor masses. The report includes the diagnostic challenges, the surgical options of sacral and/or presacral tumors, the histopathological findings, and long-term clinical and radiographic surveillance. METHODS: The patient was treated by a combination of preoperative adjuvant selective arterial embolization, radical surgical excision through an anterior approach followed by subsequent osteosynthesis and stabilization through a posterior approach. RESULTS: Clinical and radiographic follow-up for 2 years was uneventful, and the patient is still free of recurrence or any complaints. CONCLUSION: The current report documents the diagnostic and surgical challenge of a gigantic aneurysmal bone cyst of the sacrum and its successful management.

Adolescent↗

PubMed2003

Infrared analysis of the mineral and matrix in bones of osteonectin-null mice and their wildtype controls.

Osteonectin function in bone was investigated by infrared analysis of bones from osteonectin-null (KO) and wildtype mice (four each at 11, 17, and 36 weeks). An increase in mineral content and crystallinity in newly formed KO bone and collagen maturity at all sites was found using FTIR microspectroscopy and imaging; consistent with osteonectin's postulated role in regulating bone formation and remodeling. Mineral and matrix properties of tibias of osteonectin-null mice and their age- and background-matched wildtype controls were compared using Fourier-transform infrared microspectroscopy (FTIRM) and infrared imaging (FTIRI) at 10- and 7-mm spatial resolution, respectively. The bones came from animals that were 11, 17, and 36 weeks of age. Individual FTIRM spectra were acquired from 20 x 20 microm areas, whereas 4096 simultaneous FTIRI spectra were acquired from 400 x 400 microm areas. The FTIRM data for mineral-to-matrix, mineral crystallinity, and collagen maturity were highly correlated with the FTIRI data in similar regions. In general, the osteonectin-null mice bones had higher mineral contents and greater crystallinity (crystal size and perfection) than the age-matched wildtype controls. Specifically, the mineral content of the newly forming periosteal bone was increased in the osteonectin-null mice; the crystallinity of the cortical bone was decreased in all but the oldest animals, relative to the wildtype. The most significant finding, however, was increased collagen maturity in both the cortical and trabecular bone of the osteonectin-null mice. These spectroscopic data are consistent with a mechanism of decreased bone formation and remodeling.

Animals↗

PubMed2003

Precision and accuracy of peripheral quantitative computed tomography (pQCT) in the mouse skeleton compared with histology and microcomputed tomography (microCT).

UNLABELLED: pQCT was evaluated for accuracy of phenotypic characterization of mouse bone in vivo. Bones (tibia, femur, spine) of 27 animals were measured ex vivo with pQCT, microCT, and histomorphometry and of 23 mice in vivo (pQCT). pQCT yielded satisfactory in vivo precision and accuracy in skeletal characterization. INTRODUCTION: Important aspects of modern skeletal research depend on the phenotypic characterization of genetically manipulated mice, with some approaches requiring in vivo measurement. Peripheral quantitative computed tomography (pQCT) is applicable in vivo and provides opportunities to determine a large variety of bone parameters. Here we test the ex vivo and in vivo reproducibility of pQCT, and its accuracy in comparison with histomorphometry and microcomputed tomography (microCT). MATERIALS AND METHODS: We examined the tibia, femur, and lumbar spine of 27 mice ex vivo with high-resolution pQCT, using two mouse models (wild-type and ob/ob) with known differences in bone density. Measurements were repeated three times at different days in nine animals. In a second experiment, 23 animals (10 wild-type and 13 bGH transgenic mice) were repeatedly measured in vivo at 12 and 13 weeks of age, respectively. RESULTS: Among metaphyseal sites, the ex vivo precision was highest at the distal femur (RMS CV < 1% for density and < 2% for area). The correlation between density (pQCT) and bone volume fraction (histomorphometry) was r2 = 0.79 (tibia, femur, and spine), and that with microCT was r2 = 0.94 (femur). At the diaphysis, the precision was highest at the femur (< 2% for total and cortical area), and the correlation with microCT was r2 > 0.77. The in vivo precision for bone density (distal femur) was 2.3-5.1%, and that for absolute and relative cortical area (tibia) was 3.1% and 2.2%. CONCLUSIONS: The results show that pQCT can yield satisfactory precision and accuracy in skeletal characterization of mouse bones, if properly applied. The potential advantage of pQCT is that it provides a large set of parameters on bone properties and that it can be used in vivo, extending the available methodological repertoire for genetic studies.

Animals↗

PubMed2002

Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene.

Calcitonin (CT) is a known inhibitor of bone resorption. Calcitonin gene-related peptide-alpha (CGRPalpha), produced by alternative RNA processing of the CT/CGRP gene, has no clearly defined role in bone. To better understand the physiologic role of the CT/CGRP gene we created a mouse in which the coding sequences for both CT and CGRPalpha were deleted by homologous recombination. The CT/CGRP(-/-) knockout (KO) mice procreated normally, there were no identifiable developmental defects at birth, and they had normal baseline calcium-related chemistry values. However, KO animals were more responsive to exogenous human parathyroid hormone as evidenced by a greater increase of the serum calcium concentration and urine deoxypyridinoline crosslinks, an effect reversed by CT and mediated by a greater increase in bone resorption than in controls. Surprisingly, KO mice have significantly greater trabecular bone volume and a 1.5- to 2-fold increase in bone formation at 1 and 3 months of age. This effect appears to be mediated by increased bone formation. In addition, KO mice maintain bone mass following ovariectomy, whereas wild-type mice lose approximately one-third of their bone mass over 2 months. These findings argue for dual roles for CT/CGRP gene products: prevention of bone resorption in hypercalcemic states and a regulatory role in bone formation.

Alternative Splicing↗