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M E Kirchen

Publications and source records attributed to M E Kirchen.

13 recordsLinked to original sources
PubMed1999

Magnesium deficiency-induced osteoporosis in the rat: uncoupling of bone formation and bone resorption.

Magnesium (Mg) intake has been linked to bone mass and/or rate of bone loss in humans. Experimental Mg deficiency in animal models has resulted in impaired bone growth, osteopenia, and increased skeletal fragility. In order to assess changes in bone and mineral homeostasis that may be responsible, we induced dietary Mg deficiency in adult Simonsen albino rats for 16 weeks. Rats were fed either a low Mg diet (0.002 percent) or a normal control Mg diet (0.063 percent). Blood was obtained at baseline, 4 weeks, 8 weeks, 12 weeks and 16 weeks in both groups for serum Mg, calcium, PTH, and 1.25(OH)2-vitamin D determinations. Femora were harvested at 4 weeks and 16 weeks for mineral analysis and histomorphometry. Serum Mg fell in the Mg depleted group to 0.6 mg/dl (mean) by 16 weeks (controls = 2.0 mg/dl). The serum calcium (Ca) concentration was higher in the Mg depleted animals at 16 weeks, 10.8 mg/dl (controls = 8.9 mg/dl). Serum PTH concentration fell progressively in the Mg deficient rats to 30 pg/ml by week 16 (control = 96 pg/ml). Serum concentration of 1.25(OH)2-vitamin D also fell progressively in the Mg deficient animals by 16 weeks to 14 pg/ml (control = 30 pg/ml). While the percent ash weights of Ca and phosphorus in the femur were not different at any time point, the percent ash weight of Mg progressively fell to 0.54 percent vs control (0.74 percent) by 16 weeks. The percent ash weight of potassium also fell progressively in the Mg deficient group to approximately 30 percent of control by 16 weeks. Histomorphometric analyses showed a significant drop in trabecular bone volume in Mg deficient animals by 16 weeks (percent BV/TV = 13.2 percent vs 17.3 percent in controls). Evaluation of the endosteal bone surface features showed significantly greater bone resorption in the Mg depleted group as reflected in increased number of tartrate-resistant positive osteoclasts/mm bone surface (7.8 vs 4.0 in controls) and an elevated percent of bone surface occupied by osteoclasts (percent OcS/BS = 12.2 percent vs 6.7 percent in controls. This increased resorption occurred in the presence of an inappropriate lowered bone forming surface relative to controls; a decreased number of osteoblasts per mm bone surface (0.23 vs 0.94 in control) and a decrease in percent trabecular surface lined by osteoid (percent OS/BS = 0.41 vs 2.27 percent in controls) were also noted. Our findings demonstrate a Mg-deficiency induced uncoupling of bone formation and bone resorption resulting in a loss of bone mass. While the fall in PTH and/or 1.25(OH)2-D may explain a decrease in osteoblast activity, the mechanism for increased osteoclast activity is unclear. These data suggest that Mg deficiency may be a risk factor for osteoporosis.

Animals↗
PubMed1998

Magnesium deficiency induces bone loss in the rat.

Disorders in which magnesium (Mg) depletion is common have an associated high incidence of osteoporosis. Mg depletion in humans results in hypocalcemia, low serum parathyroid hormone (PTH) and 1, 25(OH)2-vitamin D levels, as well as PTH and vitamin D resistance which may serve as mechanisms for the development of osteoporosis. In order to determine if isolated Mg depletion will result in bone loss, we have induced dietary Mg deficiency in the rat. Adult (290 g) female rats were given either a low-Mg diet (2 mg/100 g chow; n = 6) or a normal control Mg diet (63 mg/100 g chow; n = 6). Dietary calcium (Ca) was normal in both groups (592 mg/100 g chow). At 12 weeks, blood was obtained for serum Mg, Ca, PTH, 1,25(OH)2-vitamin D, and osteocalcin determinations. The rats were then euthanized and the femurs obtained for mineral analysis and histomorphometry. Serum Mg in the low-Mg group was less than control (0.4 +/- 0.2 vs. 1.9 +/- 0.2 mg/dl, p < 0.001; mean +/- SD) while serum Ca was higher (11. 7 +/- 0.5 vs. 9.3 +/- 0.4 mg/dl, p < 0.001). PTH was suppressed in the Mg-deficient group (36 +/- 16 vs. 109 +/- 30 pg/ml in controls, p < 0.002). Serum 1,25(OH)2-vitamin D was also suppressed in the Mg-deficient animals (7.1 +/- 4.8 vs. 28.5 +/- 8.2 pg/ml in controls, p < 0.002). Serum osteocalcin levels were not different (19.8 +/- 2.5 ng/ml in Mg-deficient rats vs. 15.3 +/- 3.4 ng/ml in controls). While the ash weight of Ca and phosphorus in the femur did not change, the ash weight of Mg fell (low-Mg group 0.55 +/- 0.01%, controls 0.65 +/- 0.02%, p < 0.001). Histomorphometry demonstrated reduction in bone mass; the trabecular bone volume in the femur of the low-Mg group was reduced from control (7.7 +/- 0.2 vs. 13.7 +/- 1.9%, p < 0.002). A surprising new observation was an increase in osteoclast (OC) bone resorption with Mg depletion. The number of OC per millimeter bone surface was 16.9 +/- 1.3 in the low-Mg group versus 7.8 +/- 1.5 in controls (p < 0.001). The percentage of bone surface occupied by OC was 38.3 +/- 3.7 in the low-Mg group versus 17.7 +/- 2.4 in controls (p < 0.001). This increased resorption occurred with an inappropriate non-altered bone-forming surface relative to control (% osteoid surface: low-Mg group 2.4 +/- 0.7 vs. controls 2.6 +/- 0.4; % osteoid volume: low-Mg group 0.25 +/- 0.09 vs. controls 0.38 +/- 0.06; number of osteoblasts per millimeter bone surface: low-Mg group 0.9 +/- 0.3 vs controls 1.3 +/- 0.3). No increase in bone-forming surface or osteoblast number despite an increase in OC-resorbing surface and OC number strongly suggests impaired activation of osteoblasts and an uncoupling of bone formation and bone resorption. Our data demonstrate that Mg depletion in the rat alters bone and mineral metabolism which results in bone loss.

Animal Nutritional Physiological Phenomena↗
PubMed1996

Methotrexate eluted from bone cement: effect on giant cell tumor of bone in vitro.

The effectiveness of methotrexate eluted from polymethylmethacrylate on cell lines established from giant cell tumor of bone was investigated in vitro to determine the possible efficacy of this treatment. Elation of methotrexate from polymethylmethacrylate beads and boluses was shown in vitro to be dose dependent and limited by the size of the bolus. Cytocidal activity of methotrexate elated from polymethylmethacrylate beads prepared without monomer and of boluses of polymethylmethacrylate with the same dose of methotrexate prepared with monomer against 2 human giant cell tumor cell lines was statistically significant at 24 hours in culture. Statistical significance occurred at 24 hours in culture. Activity was maintained in vitro after 17 days. These experiments showed that eluted methotrexate remained effective against tumor cells after exposure to thermal changes during polymerization of polymethylmethacrylate. While extensive curettage of giant cell tumor of bone followed by filling in the defect with polymethylmethacrylate has become a common treatment, a local adjuvant is necessary to reduce further risk of local recurrence. A potential alternative to cryosurgery or instillation of phenol is the use of methotrexate impregnated polymethylmethacrylate to treat residual microscopic disease after curettage. This method may provide locally effective chemotherapy without the risks of systemic toxicities.

Antimetabolites, Antineoplastic↗
PubMed1995

Effects of microgravity on bone healing in a rat fibular osteotomy model.

Bone healing was investigated histologically in a rat fibular osteotomy model subjected to microgravity (shuttle flight STS-29) and the tail suspension microgravity simulation model. Exposure to microgravity or tail suspension occurred during the last 5 days of a 10-day healing period. Periosteal osteogenesis and the development of vascular channels in both experimental groups were similar to that observed in a weightbearing control group. Chondrogenesis was more advanced in weightbearing rats than in either flight or tail-suspended rats. Angiogenesis in the osteotomy gap was more advanced in weightbearing and tail-suspended rats than in the flight group. These findings suggest that bone healing may be impaired during space travel. Interpretation of the findings is complicated by observations that flight and suspended rats lost weight during the flight period and that suspended rats consumed less water than control rats. Tail suspension did not produce the same pattern of healing as spaceflight; therefore, long-term studies of bone healing, conducted entirely in the microgravity environment, are needed to distinguish metabolic from mechanical influences and to determine whether effective fracture consolidation will occur in the absence of gravitational forces.

Animals↗
PubMed1993

Bone remodelling in the presence of chondrosarcoma: histomorphometry.

Accurate knowledge of tissue changes near bone tumors can contribute to a better understanding of tumor behavior. We have used tumor ultrastructure and quantitative bone histomorphometry to evaluate local bone/tumor features associated with a low grade chondrosarcoma in a 39-year-old male. Three noninvolved sites and two sites near the tumor in the proximal femur were studied with bone morphometry. Bone near the tumor showed increased percent osteoid surface, percent osteoid volume and fraction of osteoid surface lined by osteoblasts compared to distant noninvolved sites. Both the number of osteoblasts and mean individual osteoblast size were significantly increased compared to noninvolved sites. Osteoclast number and percent osteoclast surface were also increased near the tumor. Ultrastructural studies of tumor tissue revealed two types of tissue: synthetic mesenchymal cells and cartilage tissue. Results indicate increased bone formation and resorption near the tumor. These local bone changes may possibly reflect responses to local tumor factors and depend on the extent of the tumor.

Adult↗
PubMed1992

Bone response to invading tumors with spindle cell components: a report of findings in two patients.

Two case studies are presented in which quantitative bone histomorphometry is used to analyze bone changes in adult patients with diagnosed spindle cell sarcoma. Three tumor-involved sites and one noninvolved site from the iliac crest of patient 1 were evaluated. In the involved sites the percentage trabecular bone volume (11.0%) and the number of osteoblasts (0.6 cell/mm2) were significantly reduced, osteoid volume was significantly increased (8.1%), and woven osteoid was present. The total eroded surface (6.8%) was also significantly increased. In the noninvolved site the number of osteoblasts was decreased and both the percentage eroded and percentage osteoclast surfaces were increased. In the femoral epicondyle specimen from patient 2 the number of osteoblasts was 27.0 cells/mm2, percentage osteoid volume was 18.4%, percentage osteoid surface was 62.9%, and osteoid thickness was 20.0 microns. In tumor-involved sites in both patients indices of active bone resorption were similar and normal. These two case studies indicate that (1) distinctive morphologic changes occur in bone invaded by spindle cell sarcoma, and that (2) changes affect bone formation to a greater extent than bone resorption. Bone alterations are probably local in nature and related to the extent and duration of tumor invasion and the influence of local tumor factor(s).

Adult↗
PubMed1988

Synovisol as an irrigant for electrosurgery of joints.

The appropriate irrigation fluid for use during arthroscopic procedures should be selected on the basis of fluid-tissue and fluid-instrumentation compatibility. This study describes a new irrigation fluid, Synovisol, that is isomolar, nonhemolytic, nonantigenic, has a low viscosity, and is nonconductive. The rabbit knee was used as a model to demonstrate the immediate and long-term (3 weeks) effects of irrigation with Synovisol compared with water, normal saline, mannitol, sorbitol, glycine, and with nonirrigated controls. Results were assessed by light- and electron-microscopic evaluation of synovium and cartilage dissected from rabbit knees. While the greatest amount of damage was seen in water-treated samples, significant effects were noted with other irrigants compared with Synovisol and controls. Long-term animals showed recovery of tissues in all cases. Systemic effects evaluated by measuring plasma glycerol levels showed a transient increase that peaked at 20 min. No hemolysis was detected and kidney morphology was normal. The physiological, electrocompatible, simplicity of formula, low cost, and long-shelf-life properties of this solution makes it a fluid uniquely suited to arthroscopy.

Animals↗
PubMed1988

Alkaline and acid phosphatase demonstration in human bone and cartilage: effects of fixation interval and methacrylate embedments.

Human bone and cartilage specimens were evaluated for acid and alkaline phosphatase localization following varying fixation periods for fresh or frozen tissue. Formalin fixations of up to 183 hr were followed by embedment in methyl methacrylate; frozen tissue was examined either without fixation or following fixation for up to 1 hr and subsequent glycol or methyl methacrylate embedding. The humeral epiphysis of a young patient with osteogenic sarcoma showed optimum acid and alkaline phosphatase localization following fixation for periods up to 15 hr and embedding in methyl methacrylate. Frozen costochondral junction from a newborn with osteogenesis imperfecta type II showed optimum acid and alkaline phosphatase localization following 30 min fixation in formalin and embedding in methyl methacrylate or after 5 min fixation and embedding in glycol methacrylate.

Acid Phosphatase↗
PubMed1987

Alteration in osteoblast cell number and cell activity in the presence of invading malignant fibrous histiocytoma.

Correct prediction of tumor behavior and interpretation of local factors in the tumor microenvironment rely in part upon accurate determination of tissue changes after tumor invasion. The authors examined local bone changes in primary malignant fibrous histiocytoma (MFH) of bone in a 59-year-old woman. Three noninvolved and three tumor-involved sites were evaluated by quantitative determinations of bone structural and dynamic features. Compared to noninvolved sites, tumor-involved bone was characterized by significantly increased osteoblast index (89.4 +/- 15.6 [mean +/- SEM] versus 7.3 +/- 6.0, P = 0.008), percent osteoid area (12.1 +/- 2.7 versus 1.2 +/- 0.5, P = 0.02), percent of trabecular surface covered by osteoid (70.0 +/- 6.0 versus 14.5 +/- 4.8, P = 0.002), and percent osteoid lined by osteoblasts (36.4 +/- 3.6 versus 3.7 +/- 3.0, P = 0.002). Bone 7.8 mm distant from invading tumor cells showed features characteristic of noninvolved sites, whereas bone completely surrounded by tumor showed markedly decreased osteoblast features. Osteoblast function also was affected by tumor; the amount of matrix laid down per day bore a significant positive correlation with the osteoblast index. These data indicate the following: distinctive bone morphologic changes occur in situ during invasion by MFH; changes affect aspects of bone formation but not resorption during invasion; both osteoblast number and osteoblast activity are significantly altered; and changes are local in nature and probably reflect the osteoblast response to local tumor factor(s) and are dependent upon the extent of tumor invasion.

Bone Neoplasms↗
PubMed1985

Improvements in dehydration and cement line staining for methacrylate embedded human bone biopsies.

Undemineralized methacrylate embedded bone biopsies and other bone specimens can be processed much more rapidly by application of acidified 2,2-dimethoxypropane (DMP) dehydration, which requires two hours, than by traditional graded ethanol dehydration, which requires at least four days. This shortened processing time is valuable when biopsy results are urgently needed to detect osteomalacia or to determine bone features prior to possible parathyroidectomy. We have processed over 200 bone specimens with DMP and have compared DMP dehydration to graded ethanol dehydration in 11 biopsies in which two plugs were available from the same patient. DMP dehydration does not compromise the following: tetracycline retention, Goldner's stain, acid phosphatase localization or histochemical identification of aluminum. Cement lines, which provide a record of past remodelling, are useful in clinical interpretation of bone biopsies. We have adapted two stains, toluidine blue and methylene blue/basic fuchsin, for improved cement line identification. Five-micrometer sections individually demineralized in acetate buffer prior to cement line staining show best results with toluidine blue at pH 5.5 and with methylene blue/basic fuchsin at pH 2.5-3.5.

Acrylates↗