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A dominantly inherited spondylometaphyseal dysplasia with "corner fractures" and congenital scoliosis.

Spondylometaphyseal dysplasia (SMD) is a term applied to a varied group of skeletal dysplasias that principally involve the spine and the metaphyses of long bones. SMD Sutcliffe or "Corner Fracture" type is characterized by short stature, developmental coxa vara, fragmented appearance of the metaphyses ("corner fractures"), abnormally shaped vertebrae, odontoid hypoplasia, and dominant inheritance. We report a family with a dominantly inherited SMD with "corner fractures" and severe, congenital scoliosis but neither coxa vara nor odontoid abnormalities. This could either represent phenotypic variability in SMD-"Corner Fracture" type, or be a new, dominantly inherited SMD. The presence of severe, congenital scoliosis and short stature is present in all members of this family, and not typically seen in SMD-"Corner Fracture" type, supporting our hypothesis that this might represent a new, dominantly inherited SMD.

Abnormalities, Multiple↗

Changes in the metaphysis and diaphysis of the femur proximal to the knee in rabbits with experimentally induced inflammatory arthritis.

We quantified the cross-sectional cortical bone area and remodeling rates in the ipsilateral femoral diaphysis and metaphysis of rabbits with carrageenan-induced inflammatory monarthritis of the knee. Although osteogenesis rates were significantly elevated (approximately threefold in diaphyses and sixfold in metaphyses), the cross-sectional bone area of the diaphysis was significantly diminished. Fivefold and sixfold increases in bone resorption rates were calculated in diaphyses and metaphyses, respectively. Other morphologic changes observed were porosity and net resorption of the anterior cortex and net accretion on the posteromedial cortex ("drift" of bone). These findings may have clinical significance with regard to the mechanisms and consequences of bone changes in patients with rheumatoid arthritis.

Animals↗

From Wolff's law to the Utah paradigm: insights about bone physiology and its clinical applications.

Efforts to understand our anatomy and physiology can involve four often overlapping phases. We study what occurs, then how, then ask why, and then seek clinical applications. In that regard, in 1960 views, bone's effector cells (osteoblasts and osteoclasts) worked chiefly to maintain homeostasis under the control of nonmechanical agents, and that physiology had little to do with anatomy, biomechanics, tissue-level things, muscle, and other clinical applications. But it seems later-discovered tissue-level mechanisms and functions (including biomechanical ones, plus muscle) are the true key players in bone physiology, and homeostasis ranks below the mechanical functions. Adding that information to earlier views led to the Utah paradigm of skeletal physiology that combines varied anatomical, clinical, pathological, and basic science evidence and ideas. While it explains in a general way how strong muscles make strong bones and chronically weak muscles make weak ones, and while many anatomists know about the physiology that fact depends on, poor interdisciplinary communication left people in many other specialties unaware of it and its applications. Those applications concern 1.) healing of fractures, osteotomies, and arthrodeses; 2.) criteria that distinguish mechanically competent from incompetent bones; 3.) design criteria that should let load-bearing implants endure; 4.) how to increase bone strength during growth, and how to maintain it afterwards on earth and in microgravity situations in space; 5.) how and why healthy women only lose bone next to marrow during menopause; 6.) why normal bone functions can cause osteopenias; 7.) why whole-bone strength and bone health are different matters; 8.) why falls can cause metaphyseal and diaphyseal fractures of the radius in children, but mainly metaphyseal fractures of that bone in aged adults; 9.) which methods could best evaluate whole-bone strength, "osteopenias" and "osteoporoses"; 10.) and why most "osteoporoses" should not have bone-genetic causes and some could have extraosseous genetic causes. Clinical specialties that currently require this information include orthopaedics, endocrinology, radiology, rheumatology, pediatrics, neurology, nutrition, dentistry, and physical, space and sports medicine. Basic science specialties include absorptiometry, anatomy, anthropology, biochemistry, biomechanics, biophysics, genetics, histology, pathology, pharmacology, and cell and molecular biology. This article reviews our present general understanding of this new bone physiology and some of its clinical applications and implications. It must leave to other times, places, and people the resolution of questions about that new physiology, and to understand the many devils that should lie in its details. (Thompson D'Arcy, 1917).

Adult↗

Bone cell populations and histomorphometric correlates to function.

A circadian context has been used to develop information about the proliferative and functional behavior of the cell populations that function to model the long bones of growing rats. We asked: Are the proliferating cells in the growth cartilages and diaphyseal bone of young adult growing rats distributed within single or multiple populations? Can cytomorphometry (TEM-C) be used to determine ultrastructural correlates to the well-defined circadian rhythm of matrix formation displayed by functionally synchronous populations of metaphyseal osteoblasts? Can TEM-C reveal changes in osteoclast ultrastructure that could index a biological rhythm for osteoclastic bone mineralysis/resorption? Kinetic results derived from multiple radiothymidine labeling (DNA synthesis) support the single population model for chondrocytes and diaphyseal osteoprogenitor cells. TEM-C studies at the midpoints of the daily light and dark spans show that osteoblast RER-membrane development and cysternal volumes are maximal at the recorded daytime peak of net collagen synthesis. The extent of metaphyseal osteoclast surface ruffling (mineralysis) is also twofold greater during the day than the night--an observation supporting the concept that bone formation and resorption activities are coupled.

Animals↗

Adaptation of cancellous bone to overloading in the adult rat: a single photon absorptiometry and histomorphometry study.

Nine-month-old female rats were subjected to right hindlimb immobilization or served as controls for 0, 2, 10, 18, and 26 weeks and were double-labeled with bone markers. The right limb was immobilized against the abdomen and considered unloaded, while the left limb was overloaded during ambulation. Single-photon absorptiometry was performed on intact femur; static and dynamic histomorphometry were performed on 20 microns thick undecalcified frontal sections of the proximal tibial metaphysis. Changes in the continuously overloaded limb was compared to that in both limbs of age-matched control animals. Single-photon absorptiometry detected increases of bone mineral density of +6%, +6%, and +5% in the proximal and +9%, +7%, and +10% in the distal femoral metaphyses after 10, 18, and 26 weeks of continuous overloading. Morphometrically, significant changes occurred in proximal tibial metaphyses compared to age-matched controls: trabecular area increased +41% and +45%, trabecular number increased +31% and +32%, and trabecular separation decreased -30% and -31% after 18 and 26 weeks of overloading. A significant increase in mineral apposition rate (+38%) was found only at 26 weeks of overloading. Insignificant decreases in both eroded and labeled bone surfaces occurred at all time periods. The histomorphometric changes indicated that increased cancellous bone mass was caused by an increase in bone formation activity (i.e., increases in mineral apposition and bone formation rates) and a decrease in remodeling space (i.e., decrease in bone eroded surface). These findings indicate that the adult skeleton can quickly adapt to the increased biomechanical needs by increasing its cancellous bone mass with an adequate structural pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Long-term osteopenic changes in cancellous bone structure in ovariectomized rats.

Cancellous bone mass decreases following ovariectomy in rodents, providing a useful model for post-menopausal bone loss in humans. This study describes and quantifies the longer-term changes in cancellous bone structure in the ovariectomized (OVX) rat. Rats were OVX or sham-OVX at 100 days of age and bones were collected 540 days later. Lumbar vertebral bodies were prepared for microradiography and structural analyses (nodal analyses and star volume analyses) of cancellous bone. Proximal humerii were prepared for scanning electron microscopy (SEM). Microradiography confirmed the loss of cancellous bone from the central spongiosa regions of the vertebral bodies and the humerii in the OVX rats. Changes in trabecular structural elements included relative increases in the number of free to free, cortical to free, cortical to node struts and decreases in the node to node struts in the OVX animals compared with controls. There were increases in average lengths of the node to free, node to node, and free to free trabecular struts in the OVX animals. The marrow star volume was increased in the OVX animals indicating a greater trabecular separation in these animals compared with controls. Viewed by SEM, metaphyseal trabeculae in the controls consisted of rods and plates but in the OVX animals the remaining trabeculae were mostly longitudinal rods with smaller transverse connecting rods. The remaining bone in the OVX animals was found in the lateral metaphyseal areas and is consistent with maintenance of the structural capacity of the bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Endothelin-1 localization in bone cells and vascular endothelial cells in rat bone marrow.

Endothelin-1 (ET-1) localization in bone cells and associated vascular endothelial cells in metaphyseal bone marrow of the rat femur was examined by a biotin-streptoavidin-horseradish peroxidase method in paraffin sections and by indirect immunogold techniques in post-embedded ultrathin sections. Mouse anti-ET-1 monoclonal antibody was used as the primary antibody. In metaphyseal bone marrow, intense immunostaining was observed over osteoclasts, osteoblasts, young osteocytes, and vascular endothelial cells. But bone and cartilage matrices and chondrocytes in the proliferating zone were negative for immunoreaction. At the subcellular level, specific immunogold labeling was localized along plasma membranes and in the cytoplasm including those of ruffled borders and clear zones of osteoclasts. Some colloidal gold particles were also detectable within pale vacuoles of osteoclasts. Immunoreactivity was also found along the plasma membranes, cisterns of rough-surfaced endoplasmic reticulum, mitochondria, and cytoplasmic matrices of osteoblasts, but was less intense than that of osteoclasts. In endothelial cells of blood capillaries in close proximity to bone cells, intense immunolabeling occurred over the cytoplasm. None of the cases examined showed accumulation of immunogold particles in the secretion granules of these cells.

Animals↗

In vivo delivery of fluoresceinated dextrans to the murine growth plate: imaging of three vascular routes by multiphoton microscopy.

Bone elongation by endochondral ossification occurs through the differentiation cascade of chondrocytes of cartilaginous growth plates. Molecules from the systemic vasculature reach the growth plate from three different directions: epiphyseal, metaphyseal, and a ring vessel and plexus associated with the perichondrium. This study is an analysis of the real-time dynamics of entrance of fluoresceinated tracers of different molecular weights into the growth plate from the systemic vasculature and tests the hypothesis that molecular weight is a key variable in the determination of both the directionality and the extent of tracer movement into the growth plate. Multiphoton microscopy was used for direct in vivo imaging of the murine proximal tibial growth plate in anesthetized 4- to 5-week-old transgenic mice with green fluorescent protein linked to the collagen II promoter. Mice were given an intracardiac injection of either fluorescein (332.3 Da) or fluoresceinated dextrans of 3, 10, 40, 70 kDa, singly or sequentially. For each tracer, directionality and rate of arrival, together with extent of movement within the growth plate, were imaged in real time. For small molecules (up to 10 kDa), vascular access from all three directions was observed and entrance was equally permissive from the metaphyseal and the epiphyseal sides. Within our detection limit (a few percent of vascular concentration), 40 kDa and larger dextrans did not enter. These results have implications both for understanding systemic and paracrine regulation of growth plate chondrocytic differentiation, as well as variables associated with effective drug delivery to growth plate chondrocytes.

Animals↗

Tumor necrosis factor prevents alendronate-induced osteoclast apoptosis in vivo by stimulating Bcl-xL expression through Ets-2.

OBJECTIVE: To investigate why bisphosphonates are less effective at preventing focal bone loss in rheumatoid arthritis (RA) patients than in those with generalized osteoporosis, and the mechanisms involved. METHODS: The response of osteoclasts to alendronate (ALN) in tumor necrosis factor-transgenic (TNF-Tg) mice that develop erosive arthritis and in wild-type littermates was studied. TNF-Tg and wild-type mice were given ALN, and the osteoclast numbers in the inflamed joints and in the long bones were compared. The expression levels of Bcl-xL in the osteoclasts of TNF-Tg and wild-type mice were examined by immunostaining. The effect of overexpression of Bcl-xL and Ets-2 proteins on ALN-induced osteoclast apoptosis was determined using an in vitro osteoclast survival assay and retrovirus transfer approach. RESULTS: ALN reduced osteoclast numbers in the metaphyses by 97%, but by only 46% in the adjacent inflamed joints. Bcl-xL expression was markedly higher in osteoclasts in the joints than in those in the metaphyses of TNF-Tg mice. Bcl-xL or Ets-2 overexpression protected osteoclasts from ALN-induced apoptosis, and TNF stimulated Bcl-xL and Ets-2 expression in osteoclasts. Overexpression of Ets-2 increased Bcl-xL messenger RNA in osteoclasts, while a dominant-negative form of the Ets-2 blocked the protective effect of Bcl-xL or TNF on ALN-induced apoptosis. CONCLUSION: The reduced efficacy of bisphosphonates to stop bone erosion in the inflamed joints of RA patients may result from local high levels of TNF up-regulating Ets-2 expression in osteoclasts, which in turn stimulates Bcl-xL expression in them and reduces their susceptibility to bisphosphonate-induced apoptosis.

Alendronate↗

Effects of 1 alpha,25- and 24R,25-dihydroxyvitamin D3 on aluminum-induced rickets in growing uremic rats.

Rats were subjected to a two-stage subtotal nephrectomy or sham operation, and treated with aluminum (Al) or both aluminum and vitamin D3 metabolites for 5 weeks with a cumulative dose of 13.6 mg aluminum. Animals were injected with 3H-thymidine and 3H-proline. The following analyses were performed: quantitative histology of tibial metaphyses and cytomorphometric electron microscopy of osteoclasts, quantitative (ICP-spectroscopy) and qualitative determination (histochemical staining) of aluminum within organs, and serum biochemistry (Ca, P, Mg, vitamin D3 metabolites, alkaline phosphatase, urea). The following new facts of the aluminum-related bone disease became evident: (a) Application of aluminum to growing uremic rats induced rickets, whose major epiphyseal growth plate changes were 1 alpha,25(OH)2D3-dependent. Addition of 1 alpha,25(OH)2D3 prevented the formation of rachitic metaphysis, but failed to prevent osteoid accumulation on epiphyseal and metaphyseal trabecular surfaces. Moreover, calcitriol produced hyperosteoidosis and osteosclerosis in the same rats. Aluminum did not alter the function of osteoblasts, while osteoclasts seemed inactivated. (b) The development of rickets was associated with suppressed serum levels of 1,25(OH)2D3, reduced phosphorus level and the high content of aluminum in the bone, kidney, and liver. The addition of 24R,25(OH)2D3 markedly exaggerated the reduction of serum levels of calcitriol. We suggested that aluminum induces rickets in growing uremic rats, which consists of two components: vitamin D refractory osteomalacia and 1 alpha,25(OH)2D3-dependent epiphyseal growth plate changes.

24,25-Dihydroxyvitamin D 3↗

Brittle bones in spontaneously diabetic female rats cannot be predicted by bone mineral measurements: studies in diabetic and ovariectomized rats.

Spontaneously diabetic BB rats were sham operated (SO) or ovariectomized (OVX) within days after onset and studied after 4, 8, and 12 weeks. Analyses included histomorphometry of proximal tibial metaphyses, biochemical analyses of humeri, DXA analyses, and biomechanical testing of femora. In SO diabetic rats, no osteoblasts, osteoid tissue, or osteoclasts were present on the trabecular bone surface, but trabecular bone volume (TBV) remained normal compared with control BB rats. The concentration of IGF-I per dry weight of humerus was decreased after 12 weeks of diabetes, whereas the concentrations of calcium and osteocalcin did not change. DXA analysis showed normal bone mineral density (BMD) at both diaphyseal and metaphyseal femoral areas. On biomechanical testing, angular deformation, energy absorption, and torsional strength of the femora were decreased after 8-12 weeks of diabetes, but stiffness was normal. Ovariectomy in diabetic rats caused a decrease in femoral BMD especially at the metaphysis, and there was a trend toward decreased TBV in the tibial metaphysis; TBV loss was less marked than in control OVX rats, however. The increase in BMD at the femoral diaphysis, measured after 12 weeks of OVX in control rats, was absent in diabetic rats. Multiple-regression analysis indicated that the presence of diabetes but not ovariectomy, weight, and mineral content correlated with decreased energy absorption, angular deformation, and strength of the femora. The data infer that the (near) absence of unmineralized bone matrix in severely diabetic rats alters bone microarchitecture and ultimately results in brittle bones, which is not predicted by BMC or BMD measurements.

Absorptiometry, Photon↗

Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats.

The purpose of this study was to determine if human parathyroid hormone-(1-38) (hPTH(1-38)) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses of female rats. The right hindlimbs of 6-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization, the rats were subcutaneously injected with 200 micrograms hPTH(1-38)/kg/day for 15 days (short-term treatment) or 75 days (longer-term treatment). Static bone histomorphometry was performed on the primary spongiosa, and both static and dynamic histomorphometry were performed on the secondary spongiosa of the right proximal tibial metaphyses. Immobilization for 30 days without treatment decreased trabecular bone area, number, and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate in the secondary spongiosa. These changes reached a new steady state thereafter. Treatment with 200 micrograms hPTH(1-38)/kg/day for 15 days, beginning 30 days after immobilization, significantly increased trabecular bone area, thickness, and number in both primary and secondary spongiosa despite continuous immobilization when compared with controls. The short-term PTH treatment (15 days) significantly increased labeling perimeter, mineral apposition rate, and tissue referent-bone formation rate in the secondary spongiosa and stimulated longitudinal bone growth as compared with the controls. Longer PTH treatment (75 days) further increased trabecular bone area, thickness, and number as compared with controls and groups given short-term PTH treatment (15 days). The bone formation indices in the secondary spongiosa of the longer-term treated rats were lower than those of the short-term treated group, but they were still higher than those of controls. Our findings indicate that PTH treatment stimulates cancellous bone formation, and restores and adds extra cancellous bone to the established, disuse-osteopenic proximal tibial metaphysis of female rats with continuously immobilized right hindlimbs. These results suggest that PTH may be useful in treating disuse-induced osteoporosis in humans.

Animals↗

Droloxifene prevents ovariectomy-induced bone loss in tibiae and femora of aged female rats: a dual-energy X-ray absorptiometric and histomorphometric study.

Our previous studies indicated that droloxifene (DRO), a tissue-specific estrogen antagonist/agonist, prevented bone loss without causing uterine hypertrophy in growing ovariectomized (OVX) rats. Using dual-energy X-ray absorptiometry (DXA) and bone histomorphometry, the current study compared the efficacy of DRO to 17 beta-estradiol (E2) in preventing OVX-induced bone loss in tibiae and femora of 19-month-old rats to determine whether DRO had similar skeletal effects as E2 in aged female rats. Sprague-Dawley female rats were OVX or sham-operated (sham) at 19 months of age. The sham-operated rats were treated with vehicle (oral), while the OVX rats were treated with vehicle (oral), E2 at 30 micrograms/kg/day (sc), or DRO at 2.5, 5, or 10 mg/kg/day (oral) for 8 weeks. Bone mineral density (BMD) of whole femora (WF), distal femoral metaphyses (DFM), femoral shafts (FS), and proximal femora (PF) was determined using DXA. Static and dynamic cancellous bone histomorphometric analyses were performed in double-labeled undecalcified longitudinal sections from proximal tibial metaphyses. Ovariectomy for 8 weeks significantly reduced the BMD of WF, DFM, FS, and PF (from -6 to -15%). Treatment with E2 completely prevented the decreases in BMD of WF and DFM and had no significant effects in BMD of FS and PF in aged OVX rats. The decrease in BMD of DFM induced by OVX was prevented by treatment with DRO at all dose levels. In addition, DRO at 10 mg/kg/day prevented OVX-induced decreases in BMD of WF, FS, and PF.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Changes in biological activity of bone cells in ovariectomized rats revealed by in situ hybridization.

Twelve-week-old female rats were ovariectomized (OVX) and compared with sham-operated control rats at 3, 5, 7, 10, 14, 30, and 60 days postoperation with respect to the expression of type I collagen and osteopontin mRNAs, as well as bone structure and the number of osteoclasts. The trabecular number and separation were significantly decreased and increased, respectively, in the metaphyseal trabecular bones of OVX rat femurs. The number of osteoclasts was significantly increased in the same region of OVX rats at 3 and 5 days postoperation. Type I collagen mRNA was expressed in osteoblasts, and osteopontin mRNA was expressed in some osteoclasts, in mononuclear cells on the bone resorption surface, and in osteocytes near the resorption surface. In the metaphyseal trabecular bone, type I collagen and osteopontin mRNA expression levels in individual cells was initially increased in OVX rats from 7 to 10 days postoperation, and this was sustained for 60 days. The number of osteopontin mRNA-expressing osteocytes was also significantly increased at 10 days postoperation, which lasted until 60 days. In the epiphysis, an increase in type I collagen mRNA expression was initially observed in OVX rats at 14 days postoperation, which lasted until 60 days. The number of osteopontin mRNA-expressing osteocytes was virtually identical until 30 days postoperation in the epiphysis. These findings indicated that the biological activities of osteoblasts and osteocytes are stimulated in bones of the OVX rat and that the response for OVX differs between the metaphysis and epiphysis. Furthermore, the number of osteopontin mRNA-expressing osteocytes was increased only in bones that tended to be resorbed after OVX. This indicates that some osteocytes were stimulated to express osteopontin mRNA by estrogen deficiency and suggests that these osteopontin mRNA-expressing osteocytes may be involved in regulation of bone metabolism.

Analysis of Variance↗

Enhancement of albumin expression in bone tissues with healing rat fractures.

The characterization of 66 kDa protein molecule, a major protein component which is produced from femoral-diaphyseal tissues with fracture healing (Igarashi and Yamaguchi [2002] Int. J. Mol. Med. 9:503-508), was investigated. Weaning rats were killed at 7 and 14 days after femoral fracture. When the femoral-diaphyseal tissues with fracture healing were cultured for 48 h in a serum-free medium, many proteins in the bone tissues were released into the medium. Analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that a protein molecule of approximately 66 kDa was markedly increased in culture medium from bone tissues with fracture healing. N-terminal sequencing of 66 kDa protein indicated that its N-terminus was identical to that of rat albumin. Western blot analysis of medium 66 kDa protein showed expression of albumin. This expression was significantly enhanced by fracture healing. The expression of albumin was seen in the diaphyseal (cortical bone) and metaphyseal (trabecular bone) tissues of rat femur. When the femoral-diaphyseal tissues obtained at 7 days after femoral fracture were cultured in a serum-free medium containing either vehicle, parathyroid hormone (1-34) (10(-7) M), insulin-like growth factor-I (10(-8) M) or zinc acexamate (10(-4) M), medium albumin was significantly increased in the presence of those bone-stimulating factors. The addition of albumin (0.5 or 1.0 mg/ml of medium) caused a significant increase in calcium and deoxyribonucleic acid contents in the femoral-diaphyseal and -metaphyseal tissues obtained from normal rats in vitro. The present study demonstrates that fracture healing induces a remarkable production of albumin which is a major protein component produced from femoral-diaphyseal tissues of rats, and that albumin has an anabolic effect on bone components.

Albumins↗

The mineral and mechanical properties of bone in chronic experimental diabetes.

The long-term effects of experimentally induced diabetes on bone were studied in eight male Lewis rats, intravenously (i.v.) injected with 65 mg/kg of streptozocin (STZ) and maintained for 12 months. Eight untreated age-matched rats served as controls. In the STZ-treated rats, experimentally induced diabetes was documented by the presence of hyperglycemia at 24 h and at 3 and 12 months. Significantly less weight was gained and less growth occurred in the STZ-treated rats despite careful attention to feeding and hydration. Mineral alterations were detected in the bones of the animals with experimental diabetes. Decreased hydroxyapatite crystal perfection, decreased Ca/P of the ash, and decreased ash content in the tibial metaphyses with increased ash content in the tibial diaphyses, was noted relative to controls. Bone osteocalcin content was increased in the metaphyses of the STZ-treated rats. While absolute measures of stiffness, torsional strength and energy absorption were decreased in the bones of the STZ-treated animals, when torsional strength and stiffness were normalized for differences in both growth and geometry, the normalized stiffness values for the diabetic bones were increased. The results suggest that in experimental diabetes certain aspects of bone mineralization are adversely affected and lead to reduced strength-related properties. However, a compensatory increase in stiffness occurs. The reason for this increase, although not known, may be related to changes in bone crystal structure.

Animals↗

Cellular turnover at the chondro-osseous junction of growth plate cartilage: analysis by serial sections at the light microscopical level.

In the distal hypertrophic cell zone of growth plate cartilage, the penetration of metaphyseal vascular endothelial cells is into the noncalcified territorial and pericellular matrices. Cellular mechanisms that promote metaphyseal vascularization are understood poorly, partly because no study has addressed the question of the time sequence of cellular interactions at the chondro-osseous junction. The purpose of the present study is to make predictions about the relative and the real time duration of cellular events during vascular invasion, including an analysis of the time sequence of death of the terminal hypertrophic chondrocyte. The data from serial section analysis at the light microscopical level of tetracycline-labeled growth plates indicate that death of the terminal hypertrophic chondrocyte occurs in discrete morphological stages characterized by rapid cellular condensation followed, within minutes, by endothelial cell penetration into the vacated lacuna. Cellular condensation lasts approximately 45 min or 18% of the time a cell spends as a terminal chondrocyte. The data also demonstrate that chondrocytic death occurs prior to invasion by vascular endothelial cells and that the chondrocytic lacuna remains empty for as long as 15 min before an endothelial cell or blood vascular cell fills the space.

Animals↗

[99mTc]diphosphonate uptake and hemodynamics in arthritis of the immature dog knee.

The relationship between [99mTc]diphosphonate uptake and bone hemodynamics was studied in canine carrageenan-induced juvenile chronic arthritis. Blood flow was determined with microspheres, plasma and red cell volumes were measured by labeled fibrinogen and red cells, and the microvascular volume and mean transit time of blood were calculated. Normal femoral epiphyses had lower central and higher subchondral blood flow and diphosphonate uptake values. Epiphyseal vascular volume was uniform, resulting in a greater transit time of blood centrally. In arthritis, blood flow and diphosphonate uptake were increased subchondrally and unaffected centrally, while epiphyseal vascular volume was increased throughout, leading to prolonged transit time centrally. The normal metaphyses had low blood flow and diphosphonate uptake values in cancellous bone and very high values in growth plates, but a large vascular volume throughout. The mean transit time therefore was low in growth plates and high in adjacent cancellous bone. Arthritis caused decreased blood flow and diphosphonate uptake in growth plates but increased vascular volume and transit time of blood. Diphosphonate uptake correlated positively with blood flow and plasma volume and negatively with red cell volume in a nonlinear fashion. Thus, changes in diphosphonate uptake and microvascular hemodynamics occur in both epiphyseal and metaphyseal bone in chronic synovitis of the immature knee. The [99mTc]diphosphonate bone scan seems to reflect blood flow, plasma volume, and red cell volume of bone.

Animals↗