Search PubMed⌕ Search

Biomedical subjects

M C Faugere

Publications and source records attributed to M C Faugere.

At least 19 recordsLinked to original sources
PubMed2001

Zinc nutritional status modifies renal osteodystrophy in uremic rats.

BACKGROUND: Previous studies from our laboratories suggested that zinc depletion reduces the circulating level of 1,25-dihydroxycholecalciferol (1,25(OH)2D, calcitriol) in calcium- and phosphorus-depleted rats with normal renal function, and rats with uremia. Since calcitriol synthesis is in part dependent on renal function, we studied levels of circulating vitamin D metabolites, PTH response, mineral balance and bone histomorphometry in animals with different zinc nutritional and renal functional status. METHODS: Fifty-eight male Sprague-Dawley rats were pair-fed zinc-replete (+) or -deplete (-) diets for two weeks. Thereafter, half of each paired group underwent nephrectomy (N), while half had sham (S) operations. Animals were observed for eight weeks after surgery. External mineral balances of zinc, calcium, phosphate and magnesium were determined before surgery, and 1, 2 and 7 weeks after surgery. Plasma creatinine, zinc, calcium, phosphorus, magnesium, 25-hydroxycholecalciferol, calcitriol and PTH were determined at sacrifice. Static and dynamic bone histomorphometry was determined by standard techniques. RESULTS: After an 8-week observation period, zinc-depleted animals had lower plasma zinc levels, and nephrectomized animals had lower creatinine clearances than respective controls at sacrifice. Plasma calcium and phosphorus concentrations were similar in all four groups at sacrifice. Plasma magnesium concentrations were similar in groups with renal insufficiency, regardless of zinc nutritional status. Plasma 25-hydroxycholecalciferol and calcitriol levels were similar in all groups. There was no difference between mean PTH concentration in sham-operated animals, regardless of zinc nutritional status. Although nephrectomized groups' PTH levels were increased compared to S controls, PTH levels were increased in +Zn/N animals compared to the -Zn/N group. Zinc-deplete groups had consistent negative net zinc balance, however, there was no consistent effect of nephrectomy on external calcium, phosphorus, or magnesium balance, when nephrectomized groups of different zinc nutritional status were compared. Nephrectomized animals had histomorphometric changes indicative of higher bone turnover and abnormal mineralization. Zinc deficiency was associated with less evidence of increased parathyroid hormone activity on bone in nephrectomized rats. CONCLUSIONS: Zinc depletion limits the increase in plasma PTH concentration and the expression of secondary hyperparathyroid bone disease during the development of renal insufficiency in the renal ablation model of uremia in rats. The mechanism underlying this effect is unknown, but may involve a direct effect of zinc on the synthesis, release, metabolic clearance, and/or action of PTH on the cellular level, on the interrelationship of calcitriol and PTH, or a direct effect of zinc on bone mineral metabolism. These data highlight the potential relevance of zinc nutritional status to mineral metabolism in patients with chronic renal insufficiency and end-stage renal disease.

Animals↗
PubMed2000

Molecular bone morphometry.

Quantitative histomorphometric assessment of bone biopsies represents a powerful and informative method for the study of metabolic bone diseases. It is the gold standard against which the noninvasive "diagnostic" markers of bone metabolism as well as newly available therapeutic modalities are tested. With the rapid progress in technology of molecular biology, identification of systemic and local biomolecules known to regulate bone metabolism can now be achieved. The study of localization, levels of expression, and synthesis of these factors in bone and its microenvironment is possible through applications of in situ hybridization histochemistry (ISHH) and immunohistochemistry (IHC). Application of ISHH allows study of specific mRNA expression. IHC determines the presence and distribution of target protein in cells. These two methodologies provide the link between the cellular processes of mRNA transcription and translation to the working protein. Combining the established bone histomorphometric techniques with ISHH and IHC elevates the study of bone to new heights, i.e., cellular and molecular mechanistic issues can now be studied.

Bone and Bones↗
PubMed1998

Two lyophilized polymer matrix recombinant human bone morphogenetic protein-2 carriers in rabbit calvarial defects.

We have developed a lyophilized bone morphogenetic protein (BMP) delivery device that can be formulated to control release over 2 to 8 weeks. Bioerodible poly (d,l lactide-co-glycolide) particles loaded with 90 micrograms recombinant human BMP-2 were suspended in either carboxymethylcellulose (CMC) or methylcellulose (MC) implants. Plain CMC and MC implants served as controls, as did a nonimplanted group. A total of 40 rabbits was evaluated histologically 2, 4, or 8 weeks after receiving circular full-thickness 15-mm calvarial defects. MC appeared to prevent prolapse of periosteum and dura into the defects and did not elicit bone growth. Addition of BMP improved the result. CMC implants appeared to encourage bone growth even in the absence of BMP. When BMP was added, new bone formed earlier. CMC may influence new bone formation because it is hydrophilic. MC is less hydrophilic and may cause undue inflammation. Either can be combined with BMP to produce unitary devices that are easy to make and use.

Animals↗
PubMed1990

Bone changes occurring early after cessation of ovarian function in beagle dogs: a histomorphometric study employing sequential biopsies.

The beagle dog model has been established by our laboratory as a useful animal model to study bone loss after cessation of ovarian function. Previously we demonstrated bone loss associated with an osteoblastic insufficiency at 4 months after ovariohysterectomy (OHX). This study was designed to evaluate by four sequential monthly bone biopsies the development and course of the histologic bone abnormalities after OHX. We found cancellous bone volume, trabecular density, and wall thickness to be decreased (p less than 0.05) and trabecular separation increased (p less than 0.05) as early as 1 month after OHX. After 2 months, there was a decrease in mineralizing surface and mineral apposition rate (p less than 0.05). Volume and surface of osteoid were increased after 3 months (p less than 0.05), and there was an increase in the number of osteoblasts (p less than 0.01). No histologic signs of increased resorption were observed during the experiment. However, the findings of low bone volume with decreased trabecular density and increased separation without a change in trabecular plate thickness 4 weeks after OHX suggest that a dramatic increase in resorption must have taken place soon after OHX. These results point to an early phase of initiation of bone loss related to hyperresorption followed by a maintenance phase of low bone mass ascriblastic insufficiency. The events that stimulate the early initiating phase after cessation of ovarian function, the factors contributing to it, and the direct demonstration of hyperresorption await further studies.

Animals↗
PubMed1990

Role of calcitriol in the management of osteoporosis.

Ovariohysterectomized Beagle dogs provide a useful model for the study of bone loss following cessation of ovarian function. Data obtained in our laboratory suggest that the sequence of events occurring after cessation of such function proceeds in two phases. The first, or "initiation," phase begins within 1 month after ovariohysterectomy (OHX). Although the number of osteoclasts is unchanged, there is an increase in trabecular separation, accompanied by a dramatic decrease in cancellous bone volume, which suggests an apparent dramatic hyperresorption. This early phase is followed by a "maintenance" phase, which commences in the second month and is related to an osteoblastic insufficiency. In another experiment, administration of 1,25(OH)2D3 corrected bone loss occurring after OHX in Beagle dogs. However, a positive balance between increased bone cell activity and decreased bone cell number was not maintained. This calls for new strategies to separate the positive effect of 1,25(OH)2D3 on bone cell activity from the negative effect on bone cell number.

Animals↗
PubMed1990

Five-year postoperative results of cemented femoral arthroplasty in patients with systemic bone disease.

To determine whether bone cellular abnormality affects the results of cemented femoral arthroplasty, 21 patients had biopsies of the iliac crest and femoral cortex at the time of surgery. Roentgenographic and histomorphometric studies were used to characterize fibrous membrane formation, cancellous bone, calcar resorption, and bone turnover. Patients with high bone turnover and decreased femoral thickness and density before surgery were at risk of developing calcar resorption and cancellous diaphyses, conditions that weaken proximal stem support and lead to early failure. These findings suggest that noncemented stems may be indicated in this group. Another group, osteoporotic patients, suffered from osteoblastic insufficiency, which may be the indication for the use of cemented stems rather than noncemented stems, which require bony ingrowth.

Aged↗
PubMed1989

1,25(OH)2D3 administration in moderate renal failure: a prospective double-blind trial.

This study represents the first randomized prospective, double-blind, placebo-controlled trial of the efficacy of 1,25(OH)2D3 on bone histology and serum biochemistry in patients with mild to moderate renal failure. Sixteen patients with chronic renal impairment (creatinine clearance 20 to 59 ml per min) received either 1,25(OH)2D3, at a dose of 0.25 to 0.5 microgram daily (eight patients), or placebo. Transiliac crest bone biopsies were performed before entrance into the study and after 12 months of experimental observation. None of the patients were symptomatic or had radiological evidence of bone disease. Of the thirteen patients who completed the study, initial serum 1,25(OH)2D levels were low in seven patients and parathyroid hormone levels were elevated in seven patients. Bone histology was abnormal in all patients. 1,25(OH)2D3 treatment was associated with a significant fall in serum phosphorus and alkaline phosphatase concentrations as well as with histological evidence of an amelioration of hyperparathyroid changes. In contrast to previous reports, no deterioration of renal function attributable to the treatment occurred, perhaps because a modest dose of 1,25(OH)2D3 was employed combined with meticulous monitoring. Further investigation is required to determine whether alternative therapeutic strategies (smaller doses or intermittent therapy) may avoid the potential for suppressing bone turnover to abnormally low levels in the long term.

Adult↗
PubMed1989

Early therapy of renal bone disease with calcitriol: a prospective double-blind study.

The value of calcitriol administration in the management and prevention of renal bone disease was studied in a prospective double-blind manner in 16 patients with chronic renal impairment (creatinine clearance 20 to 59 ml per min). They were given either calcitriol at a dose of 0.25 to 0.5 micrograms daily (eight patients), or placebo. Transiliac crest bone biopsies were performed before entrance into the study and after 12 months of experimental observation. None of the patients were symptomatic or had biochemical or radiological evidence of bone disease. Of the thirteen patients who completed the study, initial serum 1,25(OH)2D levels were low in seven patients and parathyroid hormone levels were elevated in seven patients. Bone histology was abnormal in all patients. Calcitriol treatment was associated with a significant fall in serum phosphorus concentrations and alkaline phosphatase levels as well as with histological evidence of an amelioration of hyperparathyroid changes. In contrast to previous reports, no deterioration of renal function attributable to the treatment occurred, perhaps because a modest dose of calcitriol was employed combined with meticulous monitoring. Further investigation is required to determine whether alternative therapeutic strategies (smaller doses or intermittent therapy) may avoid the potential for suppressing bone turnover to abnormally low levels in the long term.

Bone Diseases↗
PubMed1988

Aluminum-related bone disease.

Only rather recently has the biologic and pathogenetic relevance of aluminum, this most common metal come under serious scientific scrutiny. Various laboratory findings of accumulations of aluminum in the brain, kidney, liver, parathyroid glands, skeletal muscle, heart, lungs, pancreas and spleen as well as stainable aluminum in bone have spurred widespread interest in aluminum absorption and toxicity and in the mechanisms involved in the metabolism of aluminum. Since the kidney is the major excretory organ for aluminum, this report focuses on the abnormalities occurring with aluminum accumulation in the bone of patients with renal failure to determine the metabolic interrelationships of aluminum, parathyroid hormone, vitamin D, iron, and calcium. This editorial presents an overview of the most recent investigations of aluminum accumulation in humans, experimental animal models, and at the cellular level, presents the metabolic relationships known to exist as well as those strongly suggested in documented studies, and identifies those aspects of aluminum-related bone disease awaiting study in this increasingly important field of inquiry. The study outlines the metabolism of aluminum, the pathogenesis, prevalence, morbidity and mortality of aluminum-related bone disease, the histopathology of bone with aluminum accumulation, the recognized difficulties inherent in the diagnosis of aluminum-related bone disease, and the current understanding as relates to prevention and therapy.

Aluminum↗
PubMed1988

1,25-dihydroxyvitamin D3 corrects bone loss but suppresses bone remodeling in ovariohysterectomized beagle dogs.

The decrease in intestinal calcium absorption and lower blood levels of 1,25-dihydroxyvitamin D [1,25-(OH)2D3] have been implicated in the pathogenesis of postmenopausal osteoporosis. This study evaluates the effects on bone of 1,25-(OH)2D3 therapy using the ovariohysterectomized dog model. The cessation of ovarian function was ascertained by an increase in serum LH levels 4 weeks after ovariohysterectomy, and significant bone loss was revealed four months after ovariohysterectomy. The bone loss was associated with an increase in the number of bone-forming cells and a decrease in the activity of these cells. The administration of 1,25-(OH)2D3 increased the activity of the bone cells and resulted in a reversal of all abnormalities in structural parameters of bone, including cancellous bone mass, trabecular wall thickness, trabecular plate separation, trabecular plate density, and trabecular plate thickness (which increased above normal). However, 1,25-(OH)2D3 therapy was also associated with a significant decrease in the number of bone-forming cells, resulting in lower bone formation at the tissue level. The results of this study indicate that 1,25-(OH)2D3 therapy can reverse the bone loss and osteoblastic insufficiency responsible for the maintenance of negative bone balance after the cessation of ovarian function. However, this therapy has a suppressive effect on bone cell number and bone turnover. This undesired side-effect of 1,25-(OH)2D3 therapy renders a chronic therapeutic regimen inefficient for the long term management of patients with osteoporosis. Intermittent 1,25-(OH)2D3 therapy or a sequential therapy using 1,25-(OH)2D3 along with substances known to increase the number of bone-forming cells is strongly suggested by these results.

Animals↗
PubMed1988

Values of noninvasive techniques in predicting bone histology.

These studies investigate the predictive value of the newer, noninvasive techniques (i.e. CT scans, measurement of bone mineral density by photon absorptiometry, and recent serum biochemical tests such as bone Gla-protein and specific bone alkaline phosphatase) by comparing these results to those of histomorphometry after bone biopsy. Results reveal interesting correlations and lack of correlations between bone parameters and biochemical measurements and indicate that bone biopsies along with newer noninvasive techniques represent the optimal approach to patients with metabolic bone diseases.

Absorptiometry, Photon↗
PubMed1987

Oxalosis in bone causing a radiographical mimicry of renal osteodystrophy.

We report a patient on maintenance dialysis with oxalosis and radiographical signs typical of hyperparathyroid bone disease in patients with end-stage renal insufficiency. The patient underwent a subtotal parathyroidectomy. Because his bone pain worsened during long-term dialytic therapy, a bone biopsy was performed and revealed crystalline deposits in trabecules and the bone marrow characteristic of oxalate. Trabecular destruction and signs of defective mineralization of bone were also found. When the diagnosis was made, the patient had become addicted to narcotic analgesics; he died from an overdose. The case underscores the limits of skeletal radiographs for the diagnosis of oxalosis in bone. Furthermore, the radiographic findings may lead to erroneous conclusions in patients with renal osteodystrophy because the radiographic signs of oxalosis can mimic those of hyperparathyroid bone disease.

Adult↗
PubMed1987

Calcitriol, parathyroid hormone, and accumulation of aluminum in bone in dogs with renal failure.

Accumulation of aluminum in bone is a frequent finding in patients requiring chronic dialysis and is associated with considerable morbidity and/or mortality. Until now, evidence seemed to point to relatively low circulating levels of parathyroid hormone as a contributing factor, but because levels of parathyroid hormone and calcitriol are interrelated, calcitriol might be also involved. In this study we employed an animal model to evaluate the single and combined effects of parathyroid hormone and calcitriol on bone aluminum accumulation. The results show significantly less aluminum accumulation in calcitriol-replete dogs independent of the presence or absence of parathyroid hormone. These results indicate that low levels of calcitriol may play a role in the development of aluminum related bone disease. Further studies are needed to demonstrate whether administration of calcitriol in patients with renal insufficiency will prevent development of aluminum-related bone disease.

Aluminum↗