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C Edouard

Publications and source records attributed to C Edouard.

At least 37 records · Page 2Linked to original sources
PubMed1984

Impaired osteoblast function in osteoporosis: comparison between calcium balance and dynamic histomorphometry.

Osteoblast function was investigated in 27 patients with idiopathic osteoporosis. Transiliac bone biopsy specimens were taken after double labelling with tetracycline, and metabolic calcium balance was studied almost simultaneously. Many of the patients showed poor double labelling of their otherwise unremarkable trabecular osteoid, suggesting impaired formation of bone at many of these surfaces. This phenomenon was not accompanied by increased width of osteoid seams (as seen in osteomalacia), indicating that formation of the matrix and its mineralisation were in equilibrium. For the first time, highly significant positive correlations (p less than 0.01) were found between indices of bone formation, determined by labelling with tetracycline, and calcium balance. Thus some patients with osteoporosis who are rapidly losing bone have low rates of formation of trabecular bone both by individual osteoblasts and in relation to available bone surfaces. As histological indices of bone resorption also independently correlated strongly and inversely (p less than 0.01) with calcium balance the rate of initiation of new basic multicellular units by osteoclastic resorption of trabecular surfaces (or the depth of resorption at these surfaces) also appears to be an important determinant of mineral balance. The mechanisms that regulate the effective life span of mature osteoblasts require further investigation, particularly as some promising treatments that can increase trabecular bone volume in osteoporosis, such as parathyroid peptide hPTH (1-34) and sodium fluoride, must work through a reversal of osteoblastic depression.

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PubMed1984

Serum bone Gla-protein: a specific marker for bone formation in postmenopausal osteoporosis.

Mean (+/- SD) serum bone Gla-protein (BGP or osteocalcin) was normal (7.0 +/- 3.3 ng/ml) in 26 patients with untreated postmenopausal osteoporosis ( PMO ). But 9 patients had values either above (4) or below (5) the normal values obtained in 35 age-matched control women (6.9 +/- 1.25 ng/ml). Serum BGP correlated positively with relative osteoid volume, relative osteoid surfaces, tetracycline labelled surfaces, and bone formation rate but not with resorption surfaces. Based on normal values for osteoid volume, patients were classified as having high (HF, 9 patients), normal (NF, 12 patients) and low osteoid formation (LF, 5 patients). Serum BGP (+/- SEM) was significantly lower in LF group (2.7 +/- 0.9 ng/ml) and significantly higher in HF group (9.7 +/- 0.8 ng/ml) than in the NF group (7.0 +/- 0.6 ng/ml). Serum alkaline phosphatase and urinary hydroxyproline did not discriminate between these three groups and did not correlate significantly with any of the measured histomorphometric indices in biopsy specimens in these patients. Serum BGP appears to be a specific marker for bone formation and can predict the histological profile in PMO . Serum BGP might be useful in investigating patients with PMO and should be valuable in assessing the effects of treatments that increase bone formation.

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PubMed1984

Iliac bone histomorphometry in adults and children with osteogenesis imperfecta.

Histomorphometric analysis was performed on transiliac undecalcified bone biopsies taken from eight adults and four children with osteogenesis imperfecta. Double tetracycline labelling done before the biopsy allowed measurement of the calcification rate in 11 patients. The adults, as well as the children, had thin iliac cortices and considerably decreased trabecular bone volume. In addition, the calcification rate was significantly reduced. Since the thickness index of osteoid seams was low or normal in all subjects, it indicated a reduced bone formation at the cellular level. In the adults, there was no significant increase in the parameters of bone resorption or in the bone formation rates at the basic multicellular unit and the tissue levels. Thus the histomorphometric profile of iliac bone in osteogenesis imperfecta is characterised by cortical and trabecular osteoporosis with decreased activity of the individual osteoblasts. These findings would suggest the use of therapeutic agents stimulating bone formation rather than agents inhibiting bone resorption in osteogenesis imperfecta.

Adolescent↗
PubMed1984

Inhibition by diphosphonates of bone resorption induced by the Walker tumor of the rat.

An animal model is described to test the effect of diphosphonates, which are powerful antiosteolytic agents, against bone tumors. This model consists of injecting Walker tumor cells into one iliac artery of a series of rats while the contralateral artery is clamped during the injection, and waiting 7 days to obtain a significant destruction of the femur and tibia of the rats. In most of the animals, after this delay, extensive lesions are observed macroscopically by X-ray and histologically. The parenteral administration of three diphosphonates, dichloromethylene diphosphonate, ethanehydroxydiphosphonate , and aminopropanediphosphonate , at 16 and 160 mumol/kg/day, protects the bones by decreasing the extent of osteolysis. This protective effect is seen both in the tumor-injected leg and in the contralateral leg and is significant when compared to nontreated animals. The most active of the drugs was dichloromethylene-diphosphonate; ethanehydroxydiphosphonate and aminopropanediphosphonate were less active, especially when given at the higher dosage. All diphosphonates produce a marked decrease of the number of osteoclasts; ethanehydroxydiphosphonate at the higher dosage, induced a large increase of nonmineralized bone. These results are discussed in light of recent clinical work, showing that this animal model is a useful tool to test the effect of new drugs against osteolysis of cancer.

Animals↗
PubMed1984

[Comparative study of serum osteocalcin and of the histomorphometric evaluation of iliac biopsy in postmenopausal osteoporosis].

The histological examination of iliac biopsies in patients with osteoporosis shows varying stages of remodeling which cannot be detected by the usual laboratory tests. We measured the serum osteocalcin level, a new test, specific for bone, in 26 postmenopausal women with primary osteoporosis. The results were correlated to the findings of the iliac biopsy. Osteocalcin is significantly related to all the parameters of bone formation but not with bone resorption. When patients were divided into 3 groups, depending on the stage of remodeling from the biopsy, osteocalcin was significantly increased in the group with a high level of bone formation, and lowest in the group with decreased osteoblastic activity than in the group with normal remodeling. Neither the serum alkaline phosphatase nor the measurement of urinary hydroxyproline could distinguish between these group.

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PubMed1983

[Treatment of hypercalcemia of myelomatous origin with intravenous diphosphonates].

Diphosphonates were administered intravenously to 4 patients with myeloma-induced hypercalcaemia. All patients received EHDP 4.3 mg/kg/day for 3 to 8 days. One of them, whose hypercalcaemia recurred, was later treated with Cl 2 MDP 5 mg/kg i.v. for 8 days. In 2 patients EHDP infusions were followed by EHDP administered orally (5 mg/kg/d) for 3 weeks, after which transiliac bone biopsy was performed. In all patients calcemia fell from 130 +/- 14 to 99 +/- 4 mg/l at the end of the intravenous treatment, with parallel decrease in calciuria. Histomorphometric analysis of the bone biopsies showed few osteoclasts but massive infiltration with plasmocytes. In one case, EHDP probably induced a deficit in mineralization. Intravenous diphosphonates therefore proved to be rapidly effective in the treatment of hypercalcaemia due to malignancy. However prolonged administration of EHDP in high doses is not recommended, as it may result in osteomalacia.

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PubMed1983

Peripheral and axial measurements of trabecular bone density in patients suspected of idiopathic vertebral osteoporosis.

In 18 patients with idiopathic crush fracture syndrome, iliac trabecular bone volume measured in 8 mm trephine biopsies correlated well with trabecular bone density as estimated in low thoracic or high lumbar vertebrae by computed tomography (CT). The CT of trabecular bone in the radius correlated poorly with the other two measurements, but it discriminated fairly well between patients and age-matched controls. These results suggest that abnormally low trabecular bone density values in the radius may be useful in predicting some patients at risk for crush fractures, but ranking patients in order of severity of axial bone loss after they have acquired a fracture requires measurements on the spine or iliac crest.

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PubMed1983

Effects of two treatment regimes with synthetic human parathyroid hormone fragment on bone formation and the tissue balance of trabecular bone in greyhounds.

The adult greyhound was found to be similar to adult man with respect to kinetic and histomorphometric indices of calcium metabolism. The relationship between trabecular bone tissue balance and the pattern of human PTH fragment 1-34 (hPTH 1-34) administration by daily injections or continuous sc infusions was investigated in this model and the results compared to those from a clinical trial of hPTH 1-34 in involutional osteoporosis (peptide administration by single daily injections). In the dogs, the daily injection regime elevated plasma levels of immunoreactive hPTH 1-34 for no more than 4 h/day. The greyhounds so treated showed significantly increased indices of bone formation (surface osteoid, plasma alkaline phosphatase activity, and skeletal accretion rate of calcium) and resorption (number of osteoclasts, resorption surfaces). Iliac trabecular bone volume increased significantly, as it did in the patients. The infusions did not significantly increase the trabecular bone volume or the 47Ca accretion rate, two parameters which increased in parallel in dogs and patients treated successfully by daily injections. The osteoclastic surfaces, however, were clearly increased by continuous infusions, while the increases in the osteoblastic surfaces were less statistically significant. Since hPTH 1-34 may inhibit osteogenesis in Friedenstein chambers, it is possible that the increased osteoblastic activity induced by the daily injection regime in trabecular bone is dependent on the noncontinuous nature of the PTH stimulus.

Animals↗
PubMed1983

Treatment of Paget's disease of bone with ethane-1, hydroxy-1,1 diphosphonate (EHDP) at a low dosage (5 mg/kg/day).

Paget's disease of bone in 51 patients was treated with ethane-1, hydroxy-1,1 diphosphonate (EHDP) for six months at a dosage of 5 mg/kg/day. Clinically, the analgesic effect on bone pain is clear, with parallel reduction in radioisotope uptake observed by quantitative bone scintigraphy. There is also a reduction of about 70% of the excess level of serum alkaline phosphatase and total 24-hour urinary hydroxyproline. Histologically, there is a significant reduction in both the osteoclastic resorption surfaces and the number of osteoclasts. In contrast to that obtained by calcitonin, these clinical, biologic, and histologic changes continue for at least one year beyond the end of the treatment. That is the main characteristic of this treatment, of which the clinical and biologic tolerance is admittedly very satisfactory. Accumulation of osteoid tissue, which is indicative of a mineralization defect, does not appear at low dosages under the prescribed conditions. EHDP (5 mg/kg/day) can be regarded as effective treatment for some patients with Paget's disease of bone.

Adult↗
PubMed1982

Long-term effects of dichloromethylene diphosphonate (CI2MDP) on skeletal lesions in multiple myeloma.

We report the long-term effects of dichloromethylene diphosphonate (CI2MDP), an inhibitor of bone resorption, on the skeletal lesions in multiple myeloma. Thirteen patients received either CI2MDP 1600 mg/d (seven patients) or a placebo (six patients) in addition to other chemotherapy, and the effects of treatment were followed over a period of up to 18 months in a double-blind study. CI2MDP treatment resulted in a marked reduction in bone pain, with no progression of radiologic skeletal lesions during the first year. This contrasted with a clinical deterioration and the occurrence of new fractures in half of the patients receiving the placebo. Two patients with hypercalciuria and increased excretion of hydroxyproline before treatment had normalized values following CI2MDP. Finally, iliac crest bone biopsies showed a reduction in osteoclast number after CI2MDP administration. We conclude from these results that CI2MDP could be of use in preventing the bone loss that occurs in multiple myeloma.

Biopsy↗
PubMed1982

Long term effects of dichloromethylene diphosphonate in Paget's disease of bone.

Dichloromethylene diphosphonate (Cl2MDP) is a diphosphonate which markedly inhibits bone resorption. We have tested Cl2MDP in Paget's disease, a disorder characterized by increased bone remodeling. Sixty-three patients with progressive Paget's disease were treated for 6 months with Cl2MDP at daily oral doses of 400, 800, 1600, or 2400 mg. Thirty-nine patients received calcium and vitamin D supplements during treatment. patients in all treatment groups had significant reduction in serum alkaline phosphatase, urinary hydroxyproline, skeletal uptake of 99mtechnetium-diphosphonate scintiscans, and resorption parameters on iliac crest biopsy samples as assessed by quantitative histomorphometry. Treatment was well tolerated and did not induce a skeletal mineralization defect. The reduction in alkaline phosphatase and urinary hydroxyproline persisted 1 yr after withdrawal of treatment. The biochemical remission was sustained in half of the patients 2 yr after the end of treatment and was accompanied by a marked reduction of bone pain. a daily dose of 800 mg is recommended as the best of control of clinical and biochemical symptoms. The transient increase in iPTH levels observed in patients treated with Cl2MDP alone did not occur when calcium and vitamin D were added. We conclude that Cl2MDP is effective in the treatment of Paget's disease of bone and provides a prolonged response. Dietary supplementation with calcium and vitamin D is desirable to prevent secondary hyperparathyroidism.

Alkaline Phosphatase↗
PubMed1981

Effects of ethane-1 hydroxy-1, 1-diphosphonate (5 mg/kg/day dose) on quantitative bone histology in Paget's disease of bone.

The effects of ethane hydroxy diphosphonate (EHDP) on quantitative bone histology have been studied in 43 pagetic patients treated for 6 months at a dose of 5 mg/kg/day. To determine the therapeutic effects on pagetic bone and to appreciate the side effects in non-pagetic bone, the patients were biopsied either in pagetic or non-pagetic areas of the ilium before the beginning of the treatment and at 3, 6 and 9 months (i.e. 3 months post-therapy) after the inception of treatment. Tetracycline double labelling of bone was performed before biopsies in each patient to measure the calcification rate. The results demonstrate that 5 mg/kg/day EHDP given for 6 months has a marked antiosteoclastic effect which is prolonged after the cessation of treatment. Pagetic osteoclasts appear more sensitive to EHDP than normal osteoclasts. The new bone formed during treatment has a regular lamellar texture. At the same time, the high appositional rate of pagetic bone is reduced to a normal value. Marrow fibrosis is reduced along with the reduction in the osteoclast population. Thus, pagetic bone changes to bone normal in quantity, quality and metabolism. Dynamically, in nonpagetic areas, a transitory decrease of calcification rate is noted at the end of the treatment, without morphological evidence of osteomalacia, except for 2 out of 43 cases. Histologically, EHDP given at a dose of 5 mg/kg/day for 6 months appears to be an effective and safe treatment for Paget's disease of bone.

Adult↗
PubMed1981

Effects of disodium dichloromethylene diphosphonate on bone loss in paraplegic patients.

21 paraplegic patients with recent traumatic spinal cord injury were orally administered 400 (n = 7) or 1,600 (n = 7) mg/d of disodium dichloromethylene diphosphonate (Cl2MDP) and compared with a placebo group (n = 7) to test the preventive effects of the drug on acute bone loss and osteoclastic resorption. Cl2MDP therapy was initiated at a mean of 17.6 d after the onset of paraplegia. The study lasted at least 6 mo, consisting of a 3.5-mo treatment period, and a variable follow-up period. The effects of Cl2MDP were assessed by blood and urine biochemistry, bone histomorphometry on transilial samples, photon absorptiometry of the tibia and fibula, and radiomorphometry of the femur. The elevation in serum and urinary calcium and in urine hydroxyproline observed in the placebo group did not appear under treatment. With both doses of Cl2MDP there was no further decrease in the bone mineral content. In the treated groups, a smaller percentage increase in osteoclastic population was also noted when compared with the placebo group, but this difference was not significant. There was no mineralization defect induced by Cl2MDP, as shown by tetracycline double labeling. It thus appears that at doses ranging between 400 and 1,600 mg, given as early as possible, Cl2MDP can prevent or reduce the development of the acute bone loss of paraplegic patients, without adverse side effects, though it does not prevent the development of heterotopic ossification.

Adolescent↗
PubMed1980

[Treatment of Paget's disease of bone with ethane-1 hydroxy-1, 1 diphosphonate at low dosage (author's transl)].

Fifty-one patients with Paget's disease were treated during 6 months with ethane-01 hydroxy-1, 1 diphosphonate (EHDP, etidronate) in doses of 5 mg/kg/day. The drug was most effective in relieving pain, at the same time diminishing the uptake of pagetic lesions on quantitative bone scans and lowering by almost 70% the abnormally high serum alkaline phosphatase levels and 24-hour hydroxyproline urinary levels. Histologically, the resorption surfaces and the number of osteoclasts per mm2 of bone tissue were significantly reduced. On follow-up, the improvement persisted for at least one year after treatment was discontinued. EHDP was well tolerated clinically and biologically, and on histological sections no accumulation of osteoid tissue due to impaired mineralization was seen. EHDP at the 5 mg/kg/day dose appears to be effective in the treatment of Paget's disease.

Adult↗
PubMed1980

Anabolic effect of human parathyroid hormone fragment on trabecular bone in involutional osteoporosis: a multicentre trial.

After baseline studies, 21 patients with osteoporosis were treated with human parathyroid hormone fragment (PTH 1-34) given as once-daily subcutaneous injections for 6-24 months. The dose used did not cause hypercalcaemia even in the first few hours after injection. Calcium and phosphate balances improved in some patients, but there was no significant improvement in the group values. There were, however, substantial increases in iliac trabecular bone volume: the mean increase, confirmed by repeat blind measurements, was 70% above mean baseline volume. The new bone was histologically normal. Those patients who had the largest increases in 47Ca-kinetic and histomorphometric indices of new bone formation showed the greatest increases in trabecular bone volume, suggesting that treatment with human parathyroid hormone fragment caused a dissociation between formation and resorption rates that was confined to trabecular bone. Since vertebrae are four-fifths composed of trabecular bone, this hormone fragment may prove useful in treating patients with the crush fracture syndrome.

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