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Biomedical subjects

M Bergfeld

Publications and source records attributed to M Bergfeld.

9 recordsLinked to original sources
PubMed2000

Oim mice exhibit altered femur and incisor mineral composition and decreased bone mineral density.

To investigate the role of the pro alpha 2(I) collagen chains of type I collagen in mineralization we used the oim (osteogenesis imperfecta model) mouse as our model system. The oim/oim mouse (homozygous for a null mutation in its COL1A2 gene of type I collagen) fails to synthesize functional pro alpha 2(I) collagen chains, synthesizing only homotrimers of pro alpha 1(I) collagen chains. To evaluate the role of pro alpha 2(I) collagen in type I collagen structure/function in mineralized tissues, we examined age-matched oim/oim, heterozygous (oim/+), and wild-type (+/+) mouse femurs and incisors for mineral composition (calcium, phosphorus, magnesium, fluoride, sodium, potassium, and chloride) by neutron activation analyses (NAA), and bone mineral content (BMC) and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) in a longitudinal study (7 weeks to 16 months of age). NAA demonstrated that oim/oim femurs had significant differences in magnesium, fluoride, and sodium content as compared with +/+ mouse femurs, and oim/oim teeth had significant differences in magnesium content as compared to +/+ teeth. The ratio of calcium to phosphate was also significantly reduced in the oim/oim mouse femurs (1.58 +/- 0.01) compared with +/+ femurs (1.63 +/- 0.01). DEXA demonstrated that oim/oim mice had significantly reduced BMC and BMD as compared to oim/+ and +/+ mice. Serum and urine calcium, magnesium, and phosphorus levels, and Ca(47) absorption across the gut were equivalent in oim/oim and +/+ mice, with no evidence of hypercalciuria. These studies suggest that the known decreased biomechanical properties of oim/oim bone reflect both altered mineral composition as well as the decreased BMD, which further suggests that the presence of alpha2(I) chains plays an important role in mineralization.

Absorptiometry, Photon↗
PubMed1989

Spontaneous healing of jejunoileal bypass-induced osteomalacia.

We have previously reported that osteomalacia may develop in patients relatively soom after jejunoileal (JI) bypass surgery. The present study was designed to determine the course of JI bypass osteomalacia in an untreated group of patients. We performed serial iliac crest biopsies on nine patients at 46 and 79 months (mean) following operation. We found that the amount of osteoid (unmineralized bone matrix) decreased (P less than 0.05) with time, while trabecular bone mass increased (P less than 0.05). Although three patients were osteomalacic at the original biopsy, no patient had evidence of osteomalacia at the second bone biopsy. Based upon these patients, we conclude that the mineralization defect, when it occurs after JI bypass, does not cause clinically significant bone disease and does not persist late postoperatively.

Female↗
PubMed1987

Spontaneous release of interleukin 1 from human blood monocytes reflects bone formation in idiopathic osteoporosis.

Osteoporosis is a state of reduced skeletal mass characterized by various rates of bone remodeling. Multiple locally elaborated factors have been identified that appear to influence the cellular events in bone remodeling. The possible role(s) of these factors in the pathogenesis of osteoporosis is unknown. One such factor, interleukin 1 (IL-1), is of particular interest, as this protein is known to stimulate bone resorption and perhaps formation. Consequently, we have measured the spontaneous secretion of IL-1 activity by cultured peripheral blood monocytes obtained from 22 osteoporotic patients and 14 age-matched control subjects. Monocytes from osteoporotic patients produced more IL-1 than did monocytes from control subjects. When patients were grouped according to monocyte-produced IL-1 activity, dynamic parameters of bone formation, as judged by quantitative histomorphometric analysis of iliac crest bone biopsies and by circulating levels of bone 4-carboxyglutamic acid protein (BGP)--a marker of bone formation--were higher in subjects with elevated IL-1 activity; whereas, indices of bone resorption and static indices of bone formation were similar in subjects with either high or normal IL-1 activity. IL-1 activity released by peripheral blood monocytes appears to reflect bone formation rate in osteoporotic patients and may be of pathogenetic significance in a subset of individuals with osteoporosis.

Adult↗
PubMed1987

Biological effects of aluminum on normal dogs: studies on the isolated perfused bone.

Although it is well known that aluminum (Al) plays a role in the development of osteomalacia in patients with chronic renal failure, the mechanisms are not fully understood. Since the osteoblasts are the cells responsible for the formation of osteoid tissue, which is greatly affected in patients with Al-induced osteomalacia, it is possible that Al could affect the number of osteoblasts or interfere with their function. To further characterize this potential mechanism, we performed studies in isolated perfused tibiae from normal and Al-treated dogs. In this system, when PTH is added to the perfusate, cAMP, a major marker of osteoblasts, is released. The dogs were divided into two groups: control, and Al-treated (0.75 mg/kg, iv, 5 days a week for 3 months). Thereafter, the dogs were killed, and the tibiae were perfused in vitro. PTH-(1-34) (3-4 ng/ml) and 3-isobutyl-1-methylxanthine (an inhibitor of phosphodiesterase) were added to the perfusate. Basal cAMP secretion was the same in both groups of dogs. After PTH was added to the perfusate, cAMP increased to a peak of 188.2 +/- 30.6 pmol/min in the normal dogs vs. 113 +/- 8.15 in Al-treated dogs (P less than 0.05). Cumulative cAMP secretion over a 30-min period was 766 +/- 127.9 pmol in the normal dogs vs. 455.6 +/- 38.2 pmol in the experimental animals (P less than 0.05). The histological appearance of bone biopsies taken before and after Al administration are consistent with a suppressive effect of the cation on osteoblast function. In particular, the number of osteoblasts had decreased 8-fold (P less than 0.01) under the influence of Al, and tetracycline-based measurements of mineralization kinetics show that osteoblast-mediated calcification was dysfunctional (P less than 0.01-0.025). On the other hand, the histological features of the post Al treatment biopsies suggest that at some time during its administration, the cation stimulates osteoblastic activity. For example, new (woven) bone formation was present in two dogs, and in another, lamellar bone, deposited under the influence of Al, covered the entire trabecular surface. Moreover, Al-associated osteoid was deposited independent of prior resorptive activity, indicating that the cation promotes bone formation in the absence of prior resorption. In keeping with its trophic effect on matrix deposition, Al also led to extensive marrow fibrosis in five dogs, indicating that Al also stimulates the activity of fibroblasts, cells closely related to osteoblasts.(ABSTRACT TRUNCATED AT 400 WORDS)

Aluminum↗
PubMed1986

The effects of discontinuation of aluminum exposure on aluminum-induced osteomalacia.

Studies in patients on dialysis have shown that aluminum (Al) accumulation in bone plays a major role in the pathogenesis of osteomalacia. It has been suggested that deferoxamine (DFO) may be beneficial in the treatment of aluminum-induced osteomalacia. The present studies were performed in four groups of uremic rats to determine if DFO and/or discontinuation of Al administration have an effect on bone histomorphometry and blood chemistries. The groups were: 1) uremic control 2) aluminum (0.75 to 1.0 mg/rat i.p., five times a week for twelve weeks): 3) aluminum + DFO, after twelve weeks Al was discontinued and the rats received DFO (75 mg/rat two times a week for nine weeks); 4) aluminum + time, after twelve weeks Al was discontinued and the rats were sacrificed after nine weeks. High levels of Al in serum and bone and low levels of PTH were seen in rats receiving Al. Bone histology revealed Al at the mineralization front, abnormal tetracycline uptake, and an increase in osteoid. DFO treatment did not significantly change the level of Al in bone, however both DFO treatment and discontinuation of Al reversed towards normal the above described lesions. In conclusion, these studies suggest that DFO and/or discontinuation of Al administration to rats with approximately 30% of renal function greatly improve aluminum-induced osteomalacia.

Aluminum↗
PubMed1983

Altered adenosine 3',5'-monophosphate release in response to parathyroid hormone by isolated perfused bone from glucocorticoid-treated dogs.

The interaction between glucocorticoids (GC) and PTH has been suggested to play a role in the pathogenesis of GC-induced osteopenia. The present studies were designed to examine the effect of acute (5-h) or chronic (4-week) GC administration in vivo on 1) cAMP release by the isolated perfused dog tibia before (basal) and after the addition of synthetic bovine PTH-(1-34) [syn bPTH-(1-34)] (stimulated) to the perfusate in vitro, in the presence or absence of the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX; 1 mM), and 2) the percent arteriovenous difference of immunoreactive PTH across bone. Acute administration of 6 mg/kg methylprednisolone (MP) did not affect the basal release of cAMP from bone (6.9 +/- 1.6 pmol/min in control vs. 6.1 +/- 1.2 pmol/min in MP-treated animals); however, syn bPTH-(1-34) stimulated release of cAMP was higher in the MP-treated animals (45 +/- 8.1 pmol/min) than in controls (26.8 +/- 3.0 pmol/min). When IBMX was added to the perfusate, basal cAMP release was not different in control and MP-treated bone (17.2 +/- 2.1 pmol/min in control vs. 19.1 +/- 1.9 pmol/min in MP-treated bone), and syn bPTH-(1-34)-stimulated release of cAMP was equivalent in both groups. In contrast, chronic prednisone therapy lead to a decrease in both basal and PTH-stimulated release of cAMP from bone (3.1 +/- 0.4 and 6.9 +/- 1.6 pmol/min for basal, and 13.1 +/- 1.7 and 26.8 +/- 3.0 pmol/min for stimulated values, respectively). However, the percent changes from the basal levels were not different in the two groups. These results were correlated with histological studies of rib biopsies obtained from these animals, which showed evidence of osteopenia and decreased bone turnover. Neither acute nor chronic GC administration had any effect on arterio-venous differences for PTH across the bone. Thus, these studies demonstrate that 1) acute administration of MP enhances the response of bone to PTH, an effect that is not apparent in the presence of the phosphodiesterase inhibitor IBMX; and 2) chronic prednisone therapy decreased basal and PTH-stimulated cAMP release, an effect that correlated with histological evidence of decreased bone turnover.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Absence of metabolic bone disease in adult patients with the nephrotic syndrome and normal renal function.

Patients with the nephrotic syndrome and normal renal function have low levels of 25(OH)D in serum presumably due to the loss of this metabolite in the urine. Osteomalacia and hyperparathyroidism have been recently reported to occur as a consequence of those low levels of 25-hydroxyvitamin D (25OHD). We studied six patients (aged 26-52 yr) with the nephrotic syndrome (mean duration, 6.7 yr; range, 2-12 yr) and normal renal function, and evaluated their calcium, phosphorus, PTH, and vitamin D metabolite levels. Bone biopsies were obtained in all patients. The creatinine clearance ranged from 83-134 ml/min . 1.73 m2 of body surface, serum albumin was 2.65 +/- 0.42 (+/- SD) g/100 ml, and proteinuria ranged from 3.5-13.2 g/24 h. All patients had normal serum magnesium, phosphorus, ionized calcium, and alkaline phosphatase (total and bone fraction), and normal roentgenographic metabolic bone survey. Serum PTH, measured by the carboxy-terminal RIA, was 5.1 +/- 2.3 mu leq/ml (normal, 2-10), serum 250HD was 8.8 +/- 4.0 ng/ml (normal, 15-30), and 1,25-dihydroxyvitamin D3 was 38 +/- 25 pg/ml (normal, 17-58). Serum vitamin D-binding protein was 420 +/- 42 micrograms/ml (normal, 400-800). The histological appearance of bone biopsies obtained in these patients was not different from that in a group of sex- and age-matched controls. Specifically, there was no increase in the volume of osteoid (unmineralized bone), the percentage of trabecular surface covered by osteoid, or the number of osteoclasts. The cellular rate of mineralization was normal in all six patients. Thus, these data indicate that low serum levels of 250HD in patients with the nephrotic syndrome and normal renal function do not necessarily result in the development of osteomalacia and/or hyperparathyroidism.

Adult↗
PubMed1983

Exogenous hyperthyroidism with osteoporosis.

Symptomatic osteopenia accompanied by subclinical hyperthyroidism developed in three women who were receiving excess thyroid hormone medication. Excessive thyroid replacement therapy resulted in mild hypercalcemia, hyperphosphatemia, and hyperphosphatasemia associated with diffuse skeletal demineralization and multiple fractures. Nondecalcified sections of double tetracycline-labeled iliac crest bone showed an accelerated rate of bone turnover with marked osteoclastosis and resorption of the cortical as well as the trabecular bone, typical of endogenous hyperthyroidism. Since thyroid hormones are among the most frequently prescribed medications, bone loss caused by exogenous hyperthyroidism may be more common than previously recognized.

Aged↗