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Biomedical subjects

M Arlot

Publications and source records attributed to M Arlot.

At least 19 recordsLinked to original sources
PubMed2005

Trabecular bone microarchitecture after alendronate treatment of osteoporotic women.

OBJECTIVE: To compare the microarchitecture of iliac crest trabecular bone from women treated for two to three years with alendronate versus that of women treated with placebo. RESEARCH DESIGN AND METHODS: Three-dimensional micro-computed tomography (micro-CT; resolution 20 microm) and two-dimensional histomorphometry (resolution 5-7 microm) were used to examine trabecular bone from single transilial biopsies obtained at the completion of clinical trials. MAIN OUTCOME MEASURES: Microarchitectural variables, including bone volume, trabecular number, trabecular thickness, and trabecular spacing in specimens from alendronate- and placebo-treated women were examined. Three-dimensional images of trabecular bone from both groups were constructed from CT images. Correlations among variables and between techniques were also calculated. RESULTS: Eighty-eight specimens were suitable for evaluation by both techniques. As measured by two-dimensional histomorphometry, bone volume fraction (as a proportion of total volume) and trabecular thickness were significantly greater in alendronate specimens, 17.1 +/- 5.5% vs. 13.4 +/- 5.5% (p = 0.0043) and 127 +/- 29 microm vs. 109 +/- 28 microm (p = 0.0090), respectively, and trabecular spacing was significantly smaller, 729 +/- 227 microm vs. 862 +/- 338 microm (p = 0.005). Micro-CT yielded similar findings: bone volume and trabecular number were significantly greater in alendronate specimens: 19.4 +/- 6.2% vs. 16.2 +/- 6.3% (p = 0.0412) and 1.46(+/-) 0.32 vs. 1.31(+/-) 0.33 per mm (p = 0.0346). Two-dimensional and micro-CT measured characteristics correlated strongly with one another, with Pearson product moment correlation coefficients ranging from 0.60 (for trabecular thickness) to 0.83 (for bone volume). CONCLUSIONS: Trabecular microarchitecture of the ilium, whether studied by two- or three-dimensional methods, is better (greater bone volume, greater trabecular thickness, decreased trabecular spacing) after alendronate treatment than after two to three years of treatment with placebo. Bone volume in a trabecular region is strongly correlated to its microarchitecture, suggesting that bone quantity predicts values for these microarchitectural endpoints.

Aged↗
PubMed2001

[Progressive limb lengthening with a centromedullary nail versus an external fixator: experimental study in sheep].

PURPOSE OF THE STUDY: Progressive limb lengthening with an external fixator often leads to pin-related complications. A new technique allowing progressive lengthening with a centromedullary nail without external fixation has been developed. This original double-locked device consists of matching male and female components fitted with a continuous thread. Lengthening is achieved via a one-way ratchet system. Twelve back-and-forth movements produce 1.25 mm lengthening. MATERIAL AND METHODS: We tested this new device on 20 sheep and compared results with external fixation lengthening in 20 other sheep. The animals were divided into groups for sacrifice on days 5, 10, 20, 45 and 90. Serial x-ray were obtained for all animals. In the 45-day and 90-day groups, histomorphometric (trichrome goldner coloration and polarized light microscopy) and densitometric studies were also performed. Bone mineral density (BMD) was determined and bone trabecular density (BTD) and trabecular bone volume (TBV) were expressed in percent of bone trabecular surface area. RESULTS: Mean lengthening in the 45-day and 90-day groups was 39 mm for the nail and 20 mm for external fixation (1 mm/day). At 90 days, 3 sheep out of 4 had consolidated radiologically with external fixation and 2 out of 4 with the nail. BMD was slightly better for external fixation (0.811 vs 0.695/cm(2)). This difference could probably be attributed to the greater lengthening obtained with the nail. At 45 days, BMD was the same (0.6 g/cm(2)) for both devices. BTD was nearly two-fold higher for the nail compared with external fixation (59.65% vs 32.61% at 90 days), most probably due to primary bone formation. The histomorphometric study allowed an analysis of the osteoid border. Bone quality obtained in the bone regenerate with the nail was superior to that obtained with external fixation. Primary bone formation resulted from membrane ossification with direct transformation of fibroblasts into osteoblasts. CONCLUSION: This work demonstrated that progressive lengthening can be achieved with a specifically designed centromedullary nail without iterative opening of the operative site. Tolerance to this type of device and quality of the bone regenerate are altogether satisfactory.

Absorptiometry, Photon↗
PubMed1999

Effect of multiple intravenous pamidronate courses in Paget's disease of bone.

BACKGROUND: Pamidronate is a bisphosphonate whose short-term biological efficacy in Paget's disease of bone was convincingly established many years ago. A less well studied area is the efficacy of pamidronate in slowing disease progression and in preventing and treating complications. MATERIAL AND METHODS: We conducted an uncontrolled retrospective study of 79 Paget's disease patients given multiple intravenous pamidronate courses over a mean period of 45 +/- 19 months. The pamidronate dose per course was 180 mg, usually given over three days. The disease was severe and in some cases had proved refractory to other medications. Reasons for pamidronate therapy were pain or other subjective symptoms; established bone, joint, or nervous system complications; or prevention or these complications in patients with involvement of high-risk sites. RESULTS: Bone and joint pain improved under therapy, and in 78% of cases the outcome in terms of complication treatment and/or prevention was favorable. An important finding was waning of the clinical and biological effects of pamidronate as the number of courses increased. Fourteen percent of patients developed resistance to pamidronate, which seemed more closely related to disease extension than to focal lesion activity. CONCLUSION: These data suggest that a prompt return to normal of laboratory markers, most notably total alkaline phosphatase, should be sought, if needed by using higher doses than in our study.

Adult↗
PubMed1999

The effects of alendronate on bone turnover and bone quality.

During Phase III clinical trials with alendronate, biochemical and histological studies assessed bone turnover and bone quality in patients treated for 3 years. Patients were randomised in double-blind fashion to receive placebo, alendronate 5 or 10 mg/day for 3 years or 20 mg/day for 2 years followed by 5 mg/day for 1 year. All patients also received 500 mg/day of calcium carbonate. Decreases in bone resorption with alendronate preceded decreases in bone formation. After approximately 6 months of continuous treatment, a new steady state of bone turnover was attained, leading to the increase in bone density. No subsequent decrease in the rate of bone turnover or of frozen bone was noted. Alendronate treatment did not impair bone mineralisation, induce the formation of woven bone or have any other adverse effects on bone quality.

Alendronate↗
PubMed1994

Serum undercarboxylated osteocalcin correlates with hip bone mineral density in elderly women.

We previously showed that circulating undercarboxylated osteocalcin (ucOC) is elevated in elderly women and is a powerful marker of the subsequent risk of hip fracture in elderly institutionalized women (J Clin Invest 1993; 91:1769). To investigate the relationship between bone mass and ucOC, we measured bone mineral density (BMD) of the hip with dual-energy x-ray absorptiometry in 98 elderly institutionalized women, 81.4 +/- 6.0 years old. ucOC was negatively correlated with BMD at all sites (r = -0.26 to -0.38, p < 0.001 to p < 0.0001), even after exclusion of the effect of age by partial correlation (for the femoral neck, r = -0.26, p < 0.01) and after controlling for serum parathyroid hormone. BMD was significantly lower at all sites of measurement in women with elevated ucOC (> 1.65 ng/ml, upper limit of the normal range in young women) than in those with normal ucOC (for the neck, 0.58 +/- 0.13 versus 0.43 +/- 0.13 g/cm2, p < 0.001). Similar results were obtained for ucOC expressed as the fraction of total OC (ucOC%). Multiple regression showed that ucOC has the highest predictive value for BMD when including age and body weight in the equation. In summary, our data indicate that serum ucOC is an independent determinant of BMD of the hip in elderly women. The mechanism by which serum ucOC is related to bone mass is unclear and should be addressed in further studies. However, our data suggest that ucOC level may be an interesting marker in the investigation of bone status in the elderly.

Absorptiometry, Photon↗
PubMed1991

hPTH 1-34 treatment of osteoporosis with added hormone replacement therapy: biochemical, kinetic and histological responses.

Twelve patients with vertebral fracture osteoporosis were recruited into a trial of treatment with hPTH 1-34 by daily injection for 1 year combined (from the 5th month) with an anti-resorptive agent (oestrogen, n = 9; nandrolone, n = 3). Treatment outcomes were monitored by biochemical and radiotracer measurements together with histomorphometry of transiliac biopsies before and at the end of treatment following double in vivo pre-labelling with demethylchlortetracycline. Indices of whole body bone formation, obtained from the analysis of 85Sr data, showed substantial increases (P less than 0.005) for all three indices measured) while biochemical (hydroxyproline) and kinetic measurements of bone resorption showed modest and equivocal changes only. As a result calcium balance improved. Gastrointestinal calcium absorption showed a tendency to improve, while urine calcium decreased; but these changes were statistically not significant except for radiocalcium absorption in the oestrogen treated subgroup. Histomorphometry revealed substantial increases in cancellous bone volume as reported previously with hPTH 1-34 given alone. However, iliac (as distinct from whole body) indices related to bone formation and resorption appeared to have returned towards pre-treatment values by the time of the second biopsy under the influence of the anti-resorptive agent given with the hPTH 1-34. It is confirmed that hPTH 1-34 therapy can increase iliac cancellous bone mass (as well as spinal cancellous bone mass as reported earlier) without a long-term increment in whole body bone resorption, providing the hPTH is combined with an anti-resorptive agent.

Aged↗
PubMed1990

Comparative study of fluoride bioavailability following the administration of sodium fluoride alone and in combination with different calcium salts.

To assess whether an interval of a few hours would be advisable between an intake of sodium fluoride (NaF) and that of calcium salts when treating osteoporotic patients with vertebral collapse, we carried out three pharmacokinetic studies in 12 healthy fasting volunteer subjects to compare the fluoride bioavailability provided by NaF alone and NaF combined with two calcium salts. The results were as follows: (1) When NaF is accompanied by calcium, the fluoride peak level is lower and delayed. (2) Fluoride absorption varied greatly among individuals in both experiments, but none of the 6 subjects proved to be nonabsorbers. (3) The areas under the curves obtained with each of the three preparations were not significantly different, but 24-h urinary fluoride was significantly lower in volunteers receiving simultaneously NaF and calcium salts than in volunteers receiving only NaF.

Adult↗
PubMed1990

[The role of a parathyroid hormone analogue in the pathogenesis of malignant hypercalcemia].

Patients with malignant hypercalcemia can display not only an increase in bone resorption, but also changes in the renal tubular reabsorption of calcium and phosphate similar to those found in primary hyperparathyroidism. A protein of tumoral origin likely responsible for this syndrome has been described. Even if produced by another gene than parathyroid hormone, it shares a homology in the aminoterminus and seems to exert a similar spectrum of action. Besides its role in malignant hypercalcemia, this analogue may be involved in physiological regulatory processes.

Humans↗
PubMed1989

Bone resorption and circulating PTH-like bioactivity in an animal model of hypercalcaemia of malignancy.

An in vivo model of humoral hypercalcaemia of malignancy has been used to examine the role of circulating PTH-like bioactivity in the development of bone resorption and hypercalcaemia. After inoculation of cells from a renal carcinoma cell line into nude mice, circulating PTH-like bioactivity as measured by the sensitive renal and metatarsal cytochemical bioassays for PTH was elevated in only 18% and 53% of the mice respectively. Bone resorption was elevated in all the mice investigated irrespective of the level of PTH-like bioactivity. Thus, in this model, while the circulating PTH-like moiety is more potent when acting on bone, it did not correlate with the degree of bone resorption suggesting that it may not be the sole cause of the hypercalcaemia.

Animals↗
PubMed1988

Evidence for a toxic effect of aluminum on osteoblasts: a histomorphometric study in hemodialysis patients with aplastic bone disease.

To evaluate the potential role of aluminum (Al) in a subset of dialysis patients with aplastic bone disease, we have studied tetracycline-labeled bone biopsies of 32 patients (22 males and 10 females, 45-73 years) on maintenance hemodialysis. Selection criteria included normal resorption surfaces (RS) and osteoid thickness. Eleven patients (Group I) had no stainable bone Al (Al-; 61.7 +/- 7.2 years) and 21 (Group II) had stainable bone Al (Al+; 57.7 +/- 6.8 years). Serum Al was normal to slightly elevated in Group I, but significantly higher in Group II (p less than 0.01). Al surfaces (AlS), undetectable in Group I, were 67.8 +/- 17.9% in Group II. Bone Al content (BAC) was much lower in Group I than in Group II (14.8 +/- 3.7 vs. 113.8 +/- 100.2 micrograms/g, p less than 0.01), but higher in Group I than in controls (p less than 0.05). Extensive thin osteoid seams were present in Group II. AlS was correlated with OS (r = 0.56, p less than 0.001) and OV (r = 0.48, p less than 0.01). Labeled surfaces were decreased in both groups. Labeled osteoid surfaces (TLS/OS) were below 2 SD of the mean control values in 96% of patients and calcification rate (CR) was depressed below 0.20 micros/day in 44% of patients. Bone formation rate (BFR) was strikingly depressed, values being below one SD of the mean control value in 92-100% of patients at both levels and below 2 SD of the mean in 82% of patients at BMU levels. Mineralization lag time (OMP) was markedly prolonged above 2 SD of controls in 89% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Skeletal blood flow, iliac histomorphometry, and strontium kinetics in osteoporosis: a relationship between blood flow and corrected apposition rate.

In 20 untreated patients with idiopathic or postmenopausal osteoporosis, kinetic studies of skeletal blood flow (using 18F) and bone turnover (using 85Sr) were combined with dynamic histomorphometry performed on transiliac biopsies taken within 6 weeks of each other. In 8 patients the combined studies were repeated after treatment. A further 5 patients were studied only while receiving treatment. As expected, skeletal blood flow measured by 18F correlated with an index of 85Sr uptake into the exchangeable pools of bone. Additionally and independently, skeletal blood flow correlated with an index of the work rate of the osteoblasts in each multicellular unit of bone (the corrected apposition rate of Parfitt). These correlations were statistically significant in both the untreated patients (P less than 0.05) and the whole group (P less than 0.001). Further indices related to bone turnover at the level of the skeleton as a whole were significantly associated with skeletal blood flow only in the combined group.

Aged↗
PubMed1987

Intravenous disodium etidronate therapy in Paget's disease of bone and hypercalcemia of malignancy. Effects on biochemical parameters and bone histomorphometry.

Nineteen patients with Paget's disease and four patients with hypercalcemia of malignancy underwent hypocalcemic therapy with etidronate disodium (etidronate) administered intravenously. The dosage for patients with Paget's disease was 4.3 mg/kg/day, infused on each of seven consecutive days. Nine of the 19 patients also received oral etidronate 5 mg/kg/day for three months after administration of intravenous therapy. Etidronate administered orally sustained the decreases in urinary hydroxyproline produced by the infusions, whereas levels returned to pretreatment values in most patients receiving only the intravenously administered drug. Serum alkaline phosphatase levels were not reduced in the 10 patients receiving only intravenously administered etidronate, but they declined by approximately 50 percent in the nine patients who received the additional orally administered etidronate. Transiliac-crest bone biopsy specimens obtained three months after intravenous therapy revealed a regular lamellar structure, compared with the characteristic woven pattern of pagetic bone. In all four patients with hypercalcemia of malignancy, normocalcemia was achieved by the 10th day of treatment using a dosage of 4.3 mg/kg/day. Oral etidronate therapy was beneficial in maintaining normocalcemia.

Bone and Bones↗
PubMed1987

Periodic courses of human 1-34 parathyroid peptide alternating with calcitriol paradoxically reduce bone remodelling in spinal osteoporosis.

In an attempt to achieve an anabolic response in both axial and peripheral bone, we treated twelve patients with osteoporosis using human 1-34 parathyroid peptide given discontinuously. The peptide was given as seven daily subcutaneous injections followed by 21 days' treatment with 0.25 mg calcitriol orally. This regime was repeated cyclically for at least sixteen cycles, of which the first four were at a lower dose of hPTH 1-34 than used subsequently. The results of treatment were monitored by kinetic, densitometric, histomorphometric and biochemical studies performed before and during treatment. Two patients developed hPTH 1-34 binding in their plasma during treatment: this was presumed to be due to the development of antibodies. The remainder, instead of increasing their indices of bone turnover as judged by iliac bone histomorphometry, were found to have consistent reductions in trabecular resorption surfaces. The other indices of bone formation and resorption measured showed no change or comparable reductions. The small increases seen in total body calcium were consistent with 'in-filling' of deleted basic multicellular units (BMUs). Because there is no evidence that calcitriol alone causes comparable reductions in activation of bone remodelling in osteoporosis, interruption of treatment with hPTH 1-34 after 7 days may have led to a failure of the activation mechanism to proceed to the resorption stage, with a consequent overall reduction in remodelling activity. This type of treatment regime, with its calcitonin-like effect, might be effective in reducing net bone loss due to imbalance between bone formation and resorption at the BMU level, particularly in patients with increased numbers of BMUs ('high turnover' osteoporosis).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Active bone turnover of the cortico-endosteal envelope in postmenopausal osteoporosis.

We developed a computerized semiautomatic method allowing accurate measurement of bone remodeling activity of the cortico-endosteal envelope of iliac crest biopsies. Measurement of bone turnover of the cortico-endosteal and of the trabecular envelopes were performed in 33 untreated women with postmenopausal vertebral osteoporosis and in 8 age-matched normal women. In normal women, bone remodeling was not different in the trabecular and the cortico-endosteal envelopes. In contrast, osteoporotic women had a marked, significant increase of bone formation and resorption at the cortico-endosteal envelope when compared to trabecular bone. Despite this difference, bone turnover activities of both envelopes were related, as indicated by significant correlations for most parameters between both envelopes. Serum bone gla-protein, previously reported to reflect trabecular bone formation, was also highly correlated with static and dynamic assessment of bone formation of the cortico-endosteal envelope of osteoporotic women but did not reflect bone resorption. When trabecular and endosteal measurements were pooled, correlations between serum bone gla-protein and bone formation were similar or even improved. In conclusion, our data suggest that patients with postmenopausal osteoporosis have active bone turnover at the cortico-endosteal envelope which may contribute significantly to bone loss in this disease. Because the different bone envelopes react differently to various therapeutic regimens, bone turnover of the cortico-endosteal envelope should be considered when assessing the effect of new treatments.

Aged↗
PubMed1986

Quantitative analysis of T6-positive Langerhans cells in human skin cancers.

Epidermal Langerhans cells (LC) are required for antigen-presentation and for stimulating antigen-specific T cell activation. Similar functions may be important in the immune response to malignant skin tumours. Monoclonal anti-T6 antibody was used to examine LC population in basal and squamous cell carcinomas. Positive control labeling was performed with monoclonal anti-HLA-DR antibody. The number of T6-positive LC per mm2 of section was significantly decreased (p less than 0.01) in the tumour group in comparison with a sex and age-matched control group. The number of sun-exposed and covered regions was taken into consideration in each respective group. Within the tumours, LC were found more frequently in the tumour periphery and in most differentiated tumour areas (horn pearls) than in the rest of the tumour mass. T6-positive LC were rarely found in the dermis. Moreover, LC exhibited morphological changes in specimens from tumours. Staining with anti-HLA-DR antibody revealed less numerous positive cells within tumour nests than labeling with OKT6. A relationship between T6-positive LC quantities and extent of HLA-DR-positive infiltrates around tumours could not be established. These results suggest that immunological surveillance of neoantigen-bearing tumour cells may be impaired in skin cancer. A reason for the reduced LC number may be an altered microenvironment in tumour tissue.

Aged↗
PubMed1986

Serum bone Gla-protein in renal osteodystrophy: comparison with bone histomorphometry.

Serum bone Gla-protein (S-BGP) and other serum biochemical parameters, including alkaline phosphatase (S-AP) and immunoreactive PTH (S-iPTH), were measured in 42 patients undergoing chronic hemodialysis. Each patient also had a tetracycline-labeled transiliac bone biopsy, allowing correlations between the biochemical and trabecular bone histomorphometric parameters, S-BGP was markedly increased [64.0 +/- 74.8 (+/- SD) vs. 6.2 +/- 2.2 ng/ml in normal subjects] significantly correlated with S-AP (r = 0.53) and S-iPTH (r = 0.55) levels. S-BGP was significantly higher in the 14 patients with high turnover renal osteodystrophy (HT-ROD; S-BGP, 138.5 +/- 90.8 ng/ml) than in the 28 patients with low turnover (LT-ROD; S-BGP, 26.8 +/- 14.8 ng/ml). S-BGP was significantly correlated with the cellular parameters of bone resorption and formation (r = 0.57-0.69) and with the dynamic parameters of bone formation (r = 0.62-0.82). The extent of stainable bone aluminum was significantly negatively correlated with S-BGP (r = -0.51) and serum iPTH (r = -0.33), but not with S-AP. S-BGP measurement allowed better discrimination between LT-ROD and HT-ROD groups than did S-AP measurement. However, in the patients with LT-ROD, S-BGP did not discriminate between patients with or without osteomalacia. We conclude that S-BGP is a valuable marker for evaluating bone remodeling and, more specifically, the bone formation rate at the tissue level in hemodialyzed patients.

Adolescent↗
PubMed1985

Heterogeneity of fracture syndromes in postmenopausal women.

Studies were performed on 32 women with vertebral crush fractures (mean age, 65.1 yr) and 27 patients with recent hip fractures (mean age, 83.6 yr). Histomorphometric analysis of undecalcified transiliac crest biopsies revealed significant differences between the two fracture groups. Trabecular bone volume (TBV) was significantly lower in vertebral fracture than in hip fracture patients (12.0 +/- 4.4% (+/- SD) vs. 14.8 +/- 3.6%; P = 0.014), while thickness of cortices was significantly lower for hip fracture than for vertebral fracture patients (436 +/- 231 vs. 823 +/- 465 microns; P less than 0.001). The TBV and radial bone mass (measured by absorptiometry on the shaft) for the vertebral fracture group were significantly lower than age-expected values. For the patients with hip fractures, the TBV was significantly above the expected value, and radial bone mass was not significantly different from the expected value. Other quantitative histological measurements did not generally differ between the two fracture groups and were compatible with normal or increased bone remodeling. The serum PTH in the hip fracture group was significantly increased above that expected in normal women of similar age. These data demonstrate the anatomical heterogeneity of osteoporotic fracture syndromes. Patients with vertebral fractures have an early deficit of trabecular bone for their age, while those with hip fractures have a deficit of both cortical and trabecular bone compared to women of age 50 yr, but the deficit is not excessive compared to others of similar age without fractures.

Aged↗