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Biomedical subjects

D Chappard

Publications and source records attributed to D Chappard.

At least 73 records · Page 4Linked to original sources

Spontaneous multiple vertebral fractures revealed primary haemochromatosis.

The association of haemochromatosis and bone disease is well established, but osteoporotic fracture is an unusual presentation of the disease. We describe a male patient with osteoporotic fractures as a presenting feature of haemochromatosis. The bone histomorphometry showed a dramatic decrease in trabecular bone volume associated with a decrease in cortical bone thickness. Osteoblastic and osteoclastic activities were reduced without any sign of osteomalacia. Staining for iron with Perl's stain showed focal localization at the interface between mineralized trabecular bone and bone marrow. This observation leads us to review the possible mechanisms of osteoporosis.

Hemochromatosis↗

Osteoclast cytomorphometry in patients with femoral neck fracture.

In patients with femoral neck fracture, nutritional deficiencies have been shown to be common. A low calcium diet and/or a reduced vitamin D intake have been suspected to cause secondary hyperparathyroidism responsible for increased bone turn over and bone loss. Parathyroid hormone (PTH) levels are increased in these patients, data which are in accordance with the pronounced changes observed on bone biopsies reflecting a true hyperparathyroidism. We have used a cytomorphometrical approach to characterize PTH-induced changes on the osteoclastic population. Osteoclasts were detected histochemically (by tartrate resistant acid phosphatase staining) on bone biopsies from 10 control subjects, 8 patients with primary hyperparathyroidism and 10 patients with a femoral neck fracture of osteoporotic origin. The maximum Feret's diameter of each osteoclast (Oc.Le) was determined with a semiautomatic image analyzer. In all groups, the frequency distribution of Oc.Le appeared positively skewed. In both hip fractured patients and primary hyperparathyroid patients, the mode of the distribution was higher (25-30 microns) than in controls (20-25 microns). When graphically converted on a probability graph, the osteoclastic populations appeared homogeneous and well described by a lognormal distribution in the three groups. However, osteoclasts appeared similarly enlarged in the groups of patients with primary hyperparathyroidism and with femoral neck fracture. PTH has been shown to increase both the recruitment of mononucleated precursors and their fusion into larger osteoclasts than controls. In the present study, a cytomorphometric method appeared able to identify the border line hyperparathyroidism in the hip fractured patients.

Adult↗

Effects of tiludronate on bone loss in paraplegic patients.

Immobilization secondary to spinal cord injury is associated with a marked and rapid atrophy of trabecular bone (disuse osteoporosis). This is due to an early increase of osteoclastic bone resorption associated with a pronounced decreased osteoblastic bone formation. Bisphosphonates are antiosteoclastic compounds and they have been effective in preventing disuse osteoporosis. However, some of them also depress osteoblastic activity and may impair the mineralization process. Tiludronate was shown effective in reducing bone resorption in several metabolic bone diseases without inducing mineralization defects. Twenty paraplegic patients (6 females and 14 males) were randomly assigned to three groups: 6 patients entered the placebo group; 7 patients received tiludronate 200 mg/day; and 7 received 400 mg/day. Histomorphometric analysis was performed on transiliac bone biopsies before and after 3 months treatment. An insignificant decrease of bone volume was observed in the placebo group and the 200 mg group. In patients receiving 400 mg/day, a slight increase was noted. Osteoid parameters changed nonsignificantly in three groups although the 400 mg group exhibited a slight tendency to decrease osteoid volume and thickness. Eroded surfaces increased in all groups. The number of osteoclasts (identified histochemically by TRAP staining) increased in the placebo group but decreased in groups receiving tiludronate. Tiludronate appears effective in reducing bone resorption without impairing bone formation in a manner that preserved bone mass and bone cell coupling.

Adolescent↗

Excessive bone resorption in human plasmacytomas: direct induction by tumour cells in vivo.

We studied the bone resorption (BR) in 82 patients with overt plasmacytomas (PCT) by histomorphometry. All the solitary PCT and 90% of overt PCT in complete remission lacked excessive BR. In contrast, 73% of the 68 patients with active overt PCT had an excessive BR. This excessive BR was highly related to the presence of tumour cells within the bone sample. Indeed, 92% of patients with active PCT and tumour cells within the biopsy had an excessive BR. On the other hand, 70% of patients with active PCT but lacking tumour cells within the biopsy had normal BR.

Aged↗

[Male osteoporosis].

Careful examination as well as biochemical and hormonal investigations should be performed in men suffering from vertebral crush fractures, in order to detect a destructive skeletal process (multiple myeloma, bone metastatic lesions, lympho and myeloproliferative disorders), a mineralization defect (osteomalacia) or a secondary osteoporosis: primary hyperparathyroidism, hypogonadism, hyperthyroidism, renal hypercalciuria, alcoholism and tobacco smoking. The diagnosis of idiopathic osteoporosis should be made only after these causes have been excluded; the pathogenesis of the disease is unclear but risk factors have been identified: family history of osteoporosis, low dietary calcium intake, delayed puberty, ethanol use, tobacco smoking, inactive lifestyle and lean body build. Correction of risk factors, calcium supplementation, regular program of weight bearing physical activity, in some instances correction of testosterone deficiency may be of benefit to reduce bone loss. Severe osteopenia or osteoporosis may require sodium fluoride therapy.

Absorptiometry, Photon↗

Bone histomorphometry in 50 normal Tunisian subjects.

Quantitative bone histomorphometry was done on undecalcified sections of iliac crest bone specimens obtained at autopsy from 50 normal subjects (24 males and 26 females). The following parameters were measured: cortical thickness (Ct.Th), trabecular bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), osteoid volume (OV/BV), osteoid surfaces (OS/BS), osteoid thickness (O.Th) and eroded surfaces (ES/BS). There was a significant age-related decrease in BV/TV in both sexes which followed a x3 polynomial regression. A significant decrease of Tb.Th was noted in males after the fifth decade. In males, bone loss was 1.5% per decade, but in females it was 0.36% before menopausal period and 2% after. Other parameters were unrelated to age and sex.

Adolescent↗

[Electron microscopic study of a macroporous calcium phosphate ceramic implanted in an osseous site].

Cellular and tissular responses to intraosseous graft of a macroporous calcium phosphate ceramic was studied using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Twelve specimens were implanted in 6 rabbits (tibiae), taken at day 14 after implantation and processed either for TEM (6 samples) or SEM (6 samples). As early as day 14 after implantation osteogenesis so that resorption of the newly formed bone and of the biomaterial, were observed at the surface of the ceramic, inside the macropores. Osteoblasts were clearly visible and well differentiated with abundant rough endoplasmic reticulum and large Golgi zone. The resorption processes were associated with 2 types of multinucleated cells. Based on ultrastructural observations (cellular characteristics and measurement of the microporosity) it appears that incompletely differentiated osteoclast was the major cell responsible of the biodegradation of the ceramic. These results suggest that the cellular events occurring at the surface of a macroporous calcium phosphate ceramic are similar to that observed in physiological bone remodelings.

Animals↗

Osteoclastic resorption of Ca-P biomaterials implanted in rabbit bone.

The nature of the multinucleated cells involved in the resorption processes occurring inside macroporous calcium-phosphate biomaterials grafted into rabbit bone was studied using light microscopy, histomorphometric analysis, enzymatic detection of tartrate-resistant acid phosphatase (TRAP) activity, scanning, and electron microscopy. Samples were taken at days 7, 14, and 21 after implantation. As early as day 7, osteogenesis and resorption were observed at the surface of the biomaterials, inside the macropores. Resorption of both newly formed bone and calcium-phosphate biomaterials was associated with two types of multinucleated cells. Giant multinucleated cells were found only at the surface of the biomaterials; they showed a large number of nuclei, were TRAP negative, developed no ruffled border, and contained numerous vacuoles with large accumulation of mineral crystals from the biomaterials. Osteoclasts exhibited TRAP positivity and well-defined ruffled border. They were observed at the surface of both newly formed bone and biomaterials, around the implant, and inside the macropores. In contract with the biomaterials, infoldings of their ruffled border were observed between the mineral crystals, deeply inside the microporosity. The microporosity of the biomaterials (i.e., the noncrystalline spaces inside the biomaterials) increased underneath this type of cell as compared with underneath giant cells or to the depth of the biomaterials. These observations demonstrate that macroporous calcium-phosphate biomaterials implanted in bone elicit osteogenesis and the recruitment of a double multinucleated cell population having resorbing activity: giant multinucleated cells that resorb biomaterials and osteoclasts that resorb newly formed bone and biomaterials.

Animals↗

Fat in bone xenografts: importance of the purification procedures on cleanliness, wettability and biocompatibility.

Xenografting is a promising alternative to allografts and autografts. The remaining lipids in bone are known to influence the biocompatibility. A comparative study of wettability was done on standardized blocks of two biomaterials. A highly purified and defatted bovine bone graft (T650) was found to retain more water (2.06 g/block) than a less defatted biomaterial (T360, 0.3 g/block). Wettability, observed in the laboratory, may reflect an important in vivo property: the rapidity for extracellular fluids and blood cells to invade the graft and carry bone forming cells. When implanted in rabbit cancellous bone, T650 appears to be osteoconductive in a manner that allows trabecular architecture to be restored within 6 months.

Animals↗

[Biomaterials for bone filling: comparisons between autograft, hydroxyapatite and one highly purified bovine xenograft].

Bone grafts are becoming increasingly common in orthopaedics, neurosurgery and periodontology. Twenty one New Zealand rabbits were used in the present study comparing several materials usable as bone substitutes. A 4.5 mm hole was drilled in the inner femoral condyles. Holes were filled with either an autograft (from the opposite condyle), an hydroxylapatite (Bioapatite), or a highly purified bovine xenograft (T650 Lubboc). Animals were sacrificed at 1, 3 and 6 months post implantation and a quantitative analysis of newly-formed bone volume (BNF/IV) and remaining biomaterials (BMAT/IV) was done. In addition, some holes were left unfilled and served as controls. At 6 months, there was no tendency for spontaneous repair in the control animals. The autografted animals have repaired their trabecular mass and architecture within the first month. Hydroxylapatite appeared unresorbed at six months and only thin and scanty new trabeculae were observed. The xenograft induced woven bone trabeculae formation on the first month. This was associated with resorption of the material by two multinucleated cell populations. At six months, the epiphyseal architecture was restored and the biomaterial has disappeared in most cases. Xenografts appear a promising alternative to autografts and allografts, whose infectious risks and ethical problems should always be borne in mind.

Animals↗

Effect of a five-week swimming program on rat bone: a histomorphometric study.

To specify the exercise-induced changes on different skeletal sites, the effect of a 5-week endurance swim training was studied in rats. Eighteen Lyon strain (Sprague-Dawley) 5-week old female rats were divided into nine sedentary and nine swimming rats. Each swim training session was increased by 15 minutes from 2-6 hours per day. A histomorphometric study was performed at the primary and secondary spongiosa of the distal femur and at the secondary spongiosa of lumbar and thoracic vertebral bodies. After training, bone loss was observed in the secondary spongiosa of lumbar vertebral bodies (24.7%) and in the primary spongiosa of distal femur (15.2%). A tendency to bone loss was also detected in the secondary spongiosa of distal femur (10.8%), whereas no change was detected in thoracic vertebral bodies. In secondary spongiosa, bone loss was accompanied with a thinning of trabeculae. Total eroded surfaces and osteoid surfaces were significantly decreased in the three studied skeletal sites, suggesting a decreased bone turnover. The decreased thickness of osteoid seams in both lumbar vertebrae and distal femur could mean that the osteoblastic activity has also been altered at the cell level, leading to thinning of trabeculae. Five-week swim training with such duration and intensity of exercise appears unable to increase bone volume in rats and, therefore, causes adverse effects. The three studied bones seemed to adapt differently to experimental conditions. The lack of ground reaction forces induced by water immersion might have contributed to the observed bone loss. "Normal" gravity would be an important cofactor in the osteogenic effects of exercise.

Adaptation, Physiological↗

Contributions of chronological age, age at menarche and menopause and of anthropometric parameters to axial and peripheral bone densities.

Bone mineral density (BMD) was measured in 128 normal postmenopausal women at different skeletal sites: lumbar spine and proximal femur, using dual-energy X-ray absorptiometry (DXA), and the cancellous and cortical envelopes of the distal third of radius and tibia, using precise low-dose quantitative computed tomography (QCT). Multivariate analysis included chronological age, ages related to menstrual history (menopause and menarche) and anthropometric factors, e.g. height and weight, as independent predictive variables. Weight is a much-studied predictor of bone density. At sites of high bone turnover, i.e. cancellous envelope, the effect of weight appeared overshadowed by estrogen-related parameters: age-past-menopause was the first predictor of BMD in the cancellous compartment of radius and in Ward's triangle, and the number of reproductive years was the strongest predictor of BMD in the cancellous compartment of tibia and in the spine (L2-4). This suggests that in addition to menopause, the length of menstrual life should be considered as an explanation for the variations in current bone mass in postmenopausal women. At the cortical level of radius, the effect of chronological age was predominant. At the cortical level of tibia, height and weight were the best predictors of BMD. We conclude that the influence of parameters related to menstrual history is predominant in sites with mainly cancellous tissue and that anthropometric factors constitute the best predictors of BMD in the cortical sites of weight-bearing bones.

Absorptiometry, Photon↗

The critical role of interleukin-6, interleukin-1B and macrophage colony-stimulating factor in the pathogenesis of bone lesions in multiple myeloma.

Lytic bone lesions and hypercalcemia are common features of multiple myeloma. In contrast, they are exceptional in other B-cell malignancies. Myeloma bone involvement is related to an uncoupling process associating increased osteoclastic resorption with decreased bone formation. Several osteoclast-activating factors, such as interleukin-1, macrophage colony-stimulating factor, and interleukin-6, are involved in this process. However, interleukin-6, the major myeloma cell growth factor, plays a critical role in myeloma-induced bone resorption.

Bone Resorption↗

Mechanisms of bone lesions in multiple myeloma.

Lytic bone lesions and hypercalcemia are common features of multiple myeloma; however, they are exceptional in other B-cell malignancies. Myeloma bone involvement is related to an uncoupling process associating an increased osteoclastic resorption with decreased bone formation. Several osteoclast-activating factors such as interleukin-1 (IL-1), tumor necrosis factor, and interleukin-6 (IL-6) are involved in this process. IL-6, the major myeloma cell growth factor, could play a critical role in myeloma-induced bone resorption in association with other known or unknown hematopoietic growth factors, however.

Bone Resorption↗

[Bone histomorphometric study in involuted fractured osteoporosis treated with 1-ethane-1-hydroxybiphosphonate (etidronate) during one year].

The efficacy of the biphosphonate etidronate has recently been demonstrated versus the vertebral fracture rate in fractured involuted osteoporosis in the literature. However, it would appear that the increase in bone mass (measured from the calcium density) may alone account for these results. The authors undertook a histomorphometrie study in 20 patients with a group mean age of 55 years presenting recent vertebral fracture in the context of osteoporosis, in order to assess the cell changes which may affect bone quality. This factor remains the only one which can account for the reduced number of fractures. The patients received treatment with phosphorus (1,500 mg/d) for 3 days followed by etidronate (400 mg/d) for 14 days every 90 days. A permanent daily intake of 50 mg of calcium and 400 IU of vitamin D was also administered. Each patient underwent bone biopsy of the iliac wing before and after one year of treatment (4 cycles). No change in the bone mass or architectural parameters was observed. However, general slowing of the bone remodeling was found, affecting the natality and activity of the osteoforming and osteoresorbing cells. However, this remodeling which is traditionally uncoupled in osteoporosis was once more coupled. This results in a slowing of bone loss, ageing of the bone present and no change in the architecture. Thus, the diphosphonates appear to have a beneficial effect on the quality of bone rather than on its quantity. This represents a novel approach to the treatment of osteoporosis.

Aged↗

Cortical osteoclasts are less sensitive to etidronate than trabecular osteoclasts.

Acute osteoporosis after spinal cord injury is related to an early increase in osteoclastic resorption. Healthy subjects subjected to bed rest similarly increase their osteoclast number in trabecular bone. Bisphosphonates possess a highly antiosteoclastic activity. The effects of a 120 day bed rest period, with or without etidronate therapy on cortical bone were measured in 15 subjects. Cortical thickness and cortical porosity were measured on transiliac bone biopsies taken before and after the bed rest period. Osteoclasts were detected histochemically and were counted with a semiautomatic image analyzer. Cortical thickness, cortical porosity, and cortical osteoclast number were not significantly modified in subjects submitted to bed rest alone. In the etidronate-treated patients, cortical bone mass parameters were also found to be unaffected, but the most striking feature was that the osteoclast number was unchanged. Trabecular osteoclasts, on the contrary, were increased in the untreated subjects (+95.2%) but decreased in the treated subjects (-78%). Bone cells may have heterogeneous responses according to their trabecular or cortical location. Cortical osteoclasts seem to be unaffected by etidronate therapy.

Adult↗

Hyperparathyroidism in proximal femur fractures biological and histomorphometric study in 21 patients over 75 years old.

Proximal femur fractures in elderly people are more and more frequent. Falls and senile bone disorders are the risk factors of this fracture. In order to understand the mechanisms of these bone disorders, we studied 21 consecutive patients with this fracture using bone histomorphometry. Measurements of serum intact parathormone (PTH), 25-(OH)-vitamin D, 1,25-(OH) 2-vitamin D and osteocalcin have been performed in these 21 patients, included in a larger series. We excluded patients with renal failure (serum creatinine greater than 140 mumols/l), cancer, or previous metabolic bone disease. There were 19 female and 2 male patients, ranging from 75 to 96 years, (mean 84.9). We found a low frequency of cortical (2/21) and trabecular (3/21) osteoporosis. There was no case of clearcut osteomalacia. Following histomorphometric bone study, two patients showed a typical pattern of hyperparathyroidism, and in a third one, this condition seemed very likely. In these three patients who were among the oldest, and who had high levels of serum PTH, chronic renal failure and primary hyperparathyroidism could be excluded. High bone remodeling was frequent in our patients, as reflected by the enhancement of eroded surfaces (13 cases) and of osteoid thickness (7 cases). Intact PTH level was elevated in our series compared to normal values in adults (in accordance to the PTH elevation in the case control study in a larger series). These findings suggest a major role of a secondary hyperparathyroidism in senile bone disorders favoring proximal femur fractures. This hyperparathyroidism is probably secondary to mild calcium and vitamin D deficiency. It may lead to architectural bone changes favoring this fracture.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗