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Calcium homeostasis is regulated by fluxes occurring at the levels of bone, kidney and intestine, fluxes which are controlled by calciotropic hormones. Bone resorption is stimulated by parathyroid hormone and by the bioactive metabolite of vitamin D, 1,25-dihydroxyvitamin D, or calcitriol. The renal tubular capacity to reabsorb calcium is regulated by parathyroid hormone, and calcium intestinal absorption is increased by calcitriol. Any modification of extracellular calcium concentration triggers a series of hormonal homeostatic reactions, aimed at changing these fluxes and correcting thereby calcium homeostasis perturbations. The evaluation of these fluxes provides information on the pathophysiological mechanism(s) implicated. Then the determination of calciotropic hormones circulating levels allows one the confirmation of the diagnosis evoked.

Stimulation of PTH secretion and synthesis in chronic renal failure involves direct and indirect factors. The indirect ones are those contributing to a decrease of plasma ionized calcium concentration which stimulates the release of PTH (1) primarily the negative calcium balance due to the iatrogenic reduction of dietary calcium intake associated with an inadequate synthesis of calcitriol, this latter being explained by a reduction in the nephronic mass, the phosphate retention, the acidosis and the retention of uremic toxins (2) more accessorily, the physicochemical dysequilibrium induced by the late occurring hyperphosphatemia. The factors acting directly on the parathyroid gland stimulating synthesis of prepro PTH at its transcription level: not only hypocalcitriolemia but also hypocalcemia and hyperphosphatemia. The clinicoradiological manifestations appear late, mostly only after the patient has been put on dialysis. The most precocious sign is the subperiosteal resorption assessed on the hand X-rays. Therefore diagnosis of hyperparathyroidism relies mainly on the measurement of plasma concentration of intact PTH. In dialysis patients the optimal range corresponding to the best bone histology is between 1 an 3 times the upper limit of normal. No such data exist for predialysis patients. Medical treatment of hyperparathyroidism should primarily be preventive, probably in predialysis lipin patient as soon as plasma intact PTH is greater than the normal upper limit. This treatment is based primarily on the prevention of phosphate retention, of negative calcium balance and acidosis by the use of oral alkaline salts of calcium given with the meals in association with appropriate dietary protein and phosphate restriction. Native vitamin D depletion should also be prevented but use of 1 alpha OH vitamin D3 metabolites in controversial: it is reasonable to administer them only when plasma intent PTH is above 3-7 the normal upper limit and when plasma phosphate is below 1.2 in predialysis patients below 1.5 mmol/l in dialysis patients and plasma calcium remains below 2.3 mmol/l in spite of CaCO3 administration. This situation is encountered in less than 50% of the dialysis patients and rarely in predialysis patients. In dialysis patients the calcium concentration in the dialysate should be chosen in relation to the dose of oral calcium and the use of 1 alpha OH vitamin D3. The superiority of the intermittent (oral or intravenous) over the daily oral administration is not yet clinically proven. The surgical parathyroidectomy is indicated when hypercalcemia and/or hyperphosphatemia occur under medical treatment, whereas the intact PTH levels remain very high (500 pg/ml).(ABSTRACT TRUNCATED AT 400 WORDS)

Background: the citrate dialysate (CD) is increasingly used. Calcium balance and hyperparathyroidism control could be altered due to the lower concentration of ionized calcium in dialysis fluid between acetate (AD) and CD. Randomized studies are not always transposable in the real life. The aim of this prospective study is to assess clinical and biological parameters after switch from acetate to citrate dialysate in 4 self-dialysis units. Methods: 56 hemodialysis patients (63±14 years), treated in 4 self-dialysis units (one nephrologist visit and one biological evaluation per month) were switched from AD to CD. Calcium concentration was 1.5 mmol/L vs 1.75 mmol/L to ensure same calcium mass balance based on literature review. Usual monthly biological evaluations (including PTH) were performed in 4 different laboratories (close to the unit, far from the main dialysis in-center) during 6-month follow-up. Results: calcemia was not different at 6 months over citrate dialysate (2.21mmol/L versus 2.24mmol/L at M6, p=0.26). PTH was significantly lower at 6 months (462pg/mL versus 306 pg/mL, p=0.0003). 3rd generation PTH assay changed in two laboratories. Upper limit of normal range is different between the two kits. Patients KDIGO classification could be different. Using an electronic patient database, the physician is not always aware of this change. β2microglobuline decreases (30.76mg/L versus 27.01mg/L, p, Introduction : l’utilisation du citrate dans les bains d’hémodialyse (DC) est en hausse. Le contrôle de la calcémie et de la parathormone peut être altéré du fait de la plus faible teneur en calcium des dialysats au citrate qu’à l’acétate (DA) comme certaines études récentes l’ont montré. Les essais cliniques ne sont pas toujours superposables à la réalité. L’objectif de cette étude prospective est d’évaluer les paramètres clinico-biologiques avec le changement des dialysats de l’acétate au citrate dans 4 unités d’autodialyses. Méthodes : les dialysats à l’acétate de 56 patients hémodialysés (63 ans ±14) dans 4 centres d’autodialyses (avec une visite médicale et un bilan biologique par mois) ont été remplacés par des dialysats au citrate. La teneur en calcium du dialysat a été augmentée de 1,5 mmol/L à 1,75 mmol/L afin d’assurer la même balance calcique selon les données des études précédentes. Les bilans biologiques, y compris l’hormone parathyroïdienne (PTH) ont été analysés dans 4 laboratoires différents (proches de chaque unité d’auto dialyse et éloignés du centre principal) pendant 6 mois. Résultats : la calcémie n’était pas différente à 6 mois avec le dialysat au citrate (2,21 mmol/L contre 2,24 mmol/L à M6, p=0,26). La PTH était significativement plus basse à 6 mois (462 pg/mL contre 306 pg/mL, p=0,0003). Les kits de mesure de PTH 2ème et 3ème génération ont changé dans les laboratoires en 6 mois. La norme haute de la PTH est différente entre 2 kits. La β2microglobuline a tendance à diminuer à 6 mois (30,76 mg/L contre 27,01 mg/L, p

Chronic kidney disease is known to be associated with phosphate retention. The mechanisms are complex and the early increase in serum phosphate levels in chronic kidney disease is not strictly related to the dietary phosphate load or to the degree of phosphate retention. It also implicates the activity of intestinal sodium-phosphate cotransporters, the degree of bone turnover and the retention and/or phosphate release from the skeleton, and the feedback mechanisms regulating the phosphaturia. Indeed, the increase in serum phosphate levels is only a reflection of underlying complex mechanisms, and many important factors play a role including parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23), and others. Hyperphosphatemia increases the risk of cardiovascular morbidity and mortality in chronic kidney disease as well as in subjects with normal renal function. Oral phosphate binders are prescribed in patients with chronic kidney disease and in those treated by dialysis, to prevent intestinal absorption of dietary phosphate and reduce serum phosphate. In prospective observational studies, they have been shown to decrease all-cause and cardiovascular mortality risk. However, different problems have been associated with currently available phosphate binders including the induction of a positive calcium balance and impaired outcomes with calcium-based phosphate binders or increased costs with non-calcium-based phosphate binders. Iron-based phosphate binders represent a new class of phosphate binders. The aim of this article is to provide an update review of the pathophysiological mechanisms leading and maintaining elevated serum phosphate levels in patients with chronic kidney disease and patients in dialysis, and the educational, nutritional, and therapeutic strategies that can be undertaken to control the hyperphosphatemia.

Dichloromethylene diphosphonate (Clodronate) has powerful activity against osteoclasts. We studied its effects on calcium balance in patients with malignant osteolytic lesions. Ten normocalcemic patients with advanced metastatic bone disease or myeloma were evaluated in a baseline 20-day calcium balance and kinetic study. They were then randomized to a clodronate or placebo regimen, treated intravenously for two weeks and orally for a month, and finally re-evaluated in another 20-day balance and kinetic study, conducted while they were still receiving treatment. The results show that both calcium balance and calcium absorption increased from base line in the clodronate group and that these changes were significantly different from those in the placebo group. There was a marginal decrease in bone resorption in the clodronate group and no change in bone accretion. Our results suggest that clodronate may be a useful adjuvant in managing metastatic bone disease.

Autografted parathyroids in thyroparathyroidectomized rats reestablished normal calcemia, increased calciuria, but calcium balance remained unchanged. DOCA + Saline effects on calcium metabolism (calciuria and positive calcium balance both increased) are found only when parathyroid and thyroid are present.

The authors analyse the results obtained during 54 radioisotope investigations using 45Ca in 13 cases of idiopathic hypercalciuria, 12 cases of osteoporosis, 3 cases of Paget's disease, and 2 cases of osteomalacia including one of Fanconi's disease in an adult. In 12 patients, repetition of the radio-isotope test two, three or four times; permitted the authors to study the effects of the treatments administered: calcitonin, phosphate, vitamin D, parathormon, oestrogen. Calcitonin increases intestinal absorption and reduces bone reabsorption and also accretion. Phosphate greatly increases accretion and bone reabsorption in vitamin-resistant osteomalacia of adults. The synthetic fragment 1--34 of human parathormone increases accretion and reabsorption but does not modify the calcium balance. The addition of estrogen reduces reabsorption and slightly increases accretion in two osteoporotic patients producing a positive calcium balance. This method of investigation is of great interest to assess the effects of a drug on calcium metabolism and on the two processes of bone remodelling.

Diabetes has a constantly growing prevalence and leads to a number of complications such as diabetic nephropathy. A systematic screening and an adapted management are needed to limit the renal and also the cardiovascular complications linked to diabetic nephropathy. An adequate glycemic and tensional control and control of proteinuria are the priority in the care of diabetic nephropathy. Other aspects such as phospho-calcium balance, lipid panel or lifestyle changes are also important and therefore a multidisciplinary approach is essential. A better understanding of the physiopathology may lead to even more effective treatments in the future. We resume in this article the actual management of a patient suffering from diabetic nephropathy and the future treatment perspectives.

Diabetes has a constantly growing prevalence and leads to a number of complications such as diabetic nephropathy. A systematic screening and an adapted management are needed to limit the renal and also the cardiovascular complications linked to diabetic nephropathy. An adequate glycemic and tensional control and control of proteinuria are the priority in the care of diabetic nephropathy. Other aspects such as phospho-calcium balance, lipid panel or lifestyle changes are also important and therefore a multidisciplinary approach is essential. A better understanding of the physiopathology may lead to even more effective treatments in the future. We resume in this article the actual management of a patient suffering from diabetic nephropathy and the future treatment perspectives.

The lung is the organ most frequently involved by metastatic calcification. This condition is probably under-diagnosed, the patients usually being asymptomatic. This article summarizes the current knowledge concerning pulmonary metastatic calcification.The pathogenesis of pulmonary metastatic calcification is not well known, but it involves phosphate-calcium balance, renal function and pH. The most frequently encountered aetiologies are hyperparathyroidism, neoplastic bony lesions, and renal failure. The definitive diagnosis is achieved by histology, radiological examinations being insensitive. The clinical manifestations are various and can include a pulmonary restrictive syndrome, diffusion abnormalities, hypoxaemia and respiratory failure. The latter can be severe and influence the prognosis adversely: 19 cases of fatal pulmonary metastatic calcification have been reported. The treatment is aetiological and symptomatic.The prognostic factors for a poor outcome of this potentially lethal condition remain to be determined. The management of asymptomatic patients is also uncertain.Pulmonary metastatic calcification is a rare condition of complex pathogenesis. The clinical manifestations are varied, ranging from asymptomatic to severe, even fatal.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. It has various clinical features. The most commonly affected organs are the lung, the lymph nodes, the eyes and the skin. Involvement of the musculoskeletal system is far less common and may be inaugural. Articular involvement is dominated by Lofgren syndrome and acute polyarthritis. Abarticular manifestations are often confounded with arthritis. Bone locations are dominated by sarcoidosis dactylitis and osteolysis. Muscular involvement is often unknown and can appear as 3 clinical features: spread form, myositique form or pseudotumoral form. Calcium balance disturbances are dominated by hypercalcemia which is often asymptomatique, but sometimes it reveal the sarcoidosis. Treatment of rheumatologic disorders often involves non steroidal antiinflammatory drugs, corticosteroids and methotrexate. Biological therapies such as the anti-TNFa and the anti-CD20 were showed to be effective in some case reports of severe and refractory disease.

Secondary hyperparathyroidism (HPTH-II) is a major complication of chronic renal insufficiency (CRI). It affects more than 300,000 dialyzed CRI patients in the world and probably more than 3 million as yet non-dialyzed CRI patients. It results from an imbalance in the interaction between calcium, phosphorus, vitamin D and parathyroid hormone (PTH). In fact, CRI is accompanied by phosphorus retention and this accumulation of phosphorus induces an increased synthesis of FGF-23 (Fibroblast Growth Factor-23) which inhibits the activity of lalpha-hydroxylase and the synthesis of calcitriol. Moreover, the hyperphosphaturia induced by PTH and its stimulant effect on calcitriol synthesis and tubular calcium reabsorption are compromised by the reduction in the expression of the renal PTH receptor. All these changes lead to a negative calcium balance and a reduction in calcium-sensitive receptors and vitamin D receptors in parathyroid cells (CaR), thereby releasing the secretion of PTH and the proliferation of parathyroid cells. The chronic stimulation of PTH by these anomalies causes progressive hyperplasia of the parathyroid cells which may be transformed into a benign tumor with a monoclonal appearance. The usual medical treatment of HPTH-II consists in the correction of hypocalcemia by calcium salts and vitamin D and its derivatives, hyperphosphatemia by lifestyle and dietary changes and intestinal phosphorus chelating agents and metabolic acidosis. Very recently, this treatment armamentarium has been expanded by the advent of the calcimimetic agent, cinacalcet HCl. This product increases the calcium sensitivity of CaR in parathyroid cells leading to a rapid and sustained decrease in PTH secretion. However, it is still necessary to resort to surgical parathyroidectomy (PTX) when these treatments prove to be ineffective or involve risks because of adverse effects and in particular an increase in the calcium-phosphorus ion product and the occurrence or worsening of cardiovascular calcifications. The purpose of this article is to revise the current indications of PTX and to discuss changes and the current and future trends for treatment of HPTH-II by surgery alone or combined.

Some mineral waters contain minerals in such high concentrations that they can influence bone health when consumed regularly. Calcium from mineral water is readily absorbed, inhibits PTH secretion and bone resorption on the short as well as on the long term. Sodium concentrations are too low to bother, sulfates have no documented bone effect, but fluoride can in rare cases be so high that it increases bone density. Since potassium and bicarbonate lower renal calcium excretion, and since the latter improves calcium balance, mineral waters rich in bicarbonate and potassium have been tested. Indeed, they lowered renal calcium excretion and bone resorption in short and medium term trials, and they could be of particular interest in the prevention of osteoporosis in addition to calcium-rich waters.

Parathyroidectomy changes the homeostasis of calcium balance in patients under dialysis for kidney failure. The aim of this work is to value calcium needs in 20 hemodialysed patients who underwent parathyroidectomy, in the department of nephrology of UHC Ibn Rochd of Casablanca from January 1994 to June 1999. These patients, 12 women (60%) and 8 men (40%), aged between 14 and 70 years (mean=46.10+/-13.62 years). Hungry bone syndrome was noted in 8 patients and postoperative hypocalcemia in 15 (75%). Mean minimal serum calcium was 196+/-0.21 mmol/l, with clinical signs in 6 patients. Mean calcium supplement the first postoperative week was 18.1+/-0,54 g/day in the 8 patients with hungry bone syndrome and 14.28+/-0,86 g/day in the 12 remaining patients. Between 6 and 18 months postoperatively, required calcium supplementation was 4.5 to 12 g/day in patients with hungry bone syndrome compared with 3 to 6g/day at the remaining patients. Mean serum calcium remained stable between 2.16 mmol/l to the 3(rd) month and 2.48 mmol/l to the 36(th) month. Postoperative hypocalcemia remains a major concern after parathyroidectomy requiring massive substitution with calcium and active vitamin D metabolite under close supervision to spare these patients from hypercalcemia resulting from parathyroid dysfunction.

The prevalence and the clinical gravity of the various histopathological varieties of renal osteodystrophy in dialysis patients depends on the severity of both the aluminium intoxication and that of hyperparathyroidism. The prevalence of bone pains, fractures and hypercalcemias are the highest in adynamic bone diseases (ABD) with severe aluminium intoxication, then in osteitis fibrosa and mixed osteopathy, in the ABD with moderate aluminium intoxication and rare in the mild lesion in spite of similar moderate aluminium intoxication. In the absence of aluminium intoxication, hypercalcemia and hyperphosphatemia prevalence is higher only when intact PTH is more that 4 times the upper limit of normal. When PTH is between 1 and 2 folds the ULN this prevalence is null and bone mineral density is the highest. 2. The low turnover aluminic bone diseases (osteomalacic or adynamic) will be cured by long term deferoxamine treatment. The hazards of such treatment justify the performance of a bone biopsy to ensure the diagnosis. Their prevention relies on adequate treatment of tapwater and definitive exclusion of long term administration of aluminum phosphate binders. 3. Non aluminic osteomalacia will be treated according to the same guidelines given for the uremic patients before dialysis. 4. Non aluminic adynamic bone disease will be cured by means aiming at stimulating PTH secretion as discontinuing 1 alpha hydroxylated vitamin D derivatives, and, if there is no hyperphosphatemia by discontinuation of calcium supplement. In case of hyperphosphatemia in dialysis patients CaCO3 doses have to be nevertheless increased after the dialysate calcium concentration (DCa) has been decreased in order to induce a negative perdialytic calcium balance for PTH secretion stimulation. In the near future substitution of CaCO3 by non calcemic non aluminic phosphate binders will suffice. 5. Osteitis fibrosa due to hyperparathyroidism will be treated first by securing an optimal vitamin D repletion (bringing plasma 25OH vitamin D around 30 and 60 ng/ml or 75-150 nmol/l) and by correcting hypocalcemia and hyperphosphatemia by CaCO3 at high doses (3-12 g/day) taken with the meals. In case of hypercalcemia dialysate calcium concentration will be decreased to correct it or, in a near future, CaCO3 will be decreased to 3 g/day and hyperphosphatemia will be controlled by non calcemic, non aluminic phosphate binders. When hyperphosphatemia is controlled whereas plasma calcium is normal or low, 1 alpha hydroxylated vitamin D derivatives can be administered. 6. Instrumental parathyroidectomy should be considered when plasma levels of intact PTH remain above 7 folds the upper limit of normal whereas hyperphosphatemia persists and hypercalcemia occurs in order to prevent thining of the corticals and subsequent fracture risk. In case of previous exposition to aluminum, a deferoxamine test and/or a bone biopsy will be performed to decide a long term DFO treatment before the parathyroidectomy in order to prevent the transformation of a mixed osteopathy into an aluminic adynamic bone disease. 7. The difficulty of hyperparathyroidism control in dialysis patients is due to poor compliance to phosphate binders and to irreversible parathyroid hyperplasia with occured before the dialysis stage. This stress the primary importance if its early prevention without iatrogenia by first CaCO3 and vitamin D repletion, as soon as the creatinine clearance decreases below 60 ml/min/1.73 m2.

1. 1 alpha (OH) vitamin D3 derivatives have an inconstant long term inhibitory effect on PTH secretion. As a matter of fact they act by three mechanisms, one of these being antagonistic: 1) a direct inhibitory action on the prepro-PTH gene; 2) an indirect inhibitory action by increasing plasma calcium; 3) an indirect stimulatory action by increasing plasma phosphate. These two latter phenomena are due to the stimulation of the intestinal absorption of these ions as well as to an intrinsic osteolytic action which may override the inhibition of the bone release of these ions in relation with the decrease of the PTH plasma levels. 2. The use of 1 alpha (OH)D3 derivatives in patients on chronic dialysis is justified in about 30% of the patients on dialysis when in spite of native vitamin D repletion and adequate predialysis control of plasma calcium (2.5 +/- 2 mmol/l) and of plasma phosphate (1.4 - 1.7 mmol/l), the PTH plasma levels are 3 or 5 fold the upper limit of normal whether the patient is on hemodialysis or on CAPD. When hyperphosphatemia is1.7 mmol/l it is first necessary to correct it by the use of higher doses of alkaline calcium salts given with the meals as phosphate binder together with a negative perdialytic calcium balance induced by a lower dialysate calcium in order to avoid hypercalcemia. Control of hyperphosphatemia is indeed a necessary prerequisite for the long term PTH suppressive efficacy of 1 alpha OH vitamin D derivatives. 3. The use of 1 alpha(OH)D3 derivatives in the treatment of the predialysis uremic patients is even more limited because there is no additional mean to decrease the risk of hypercalcemia when oral calcium is used as phosphate binder because of the danger of aluminum and magnesium phosphate binders. Fortunately in the adult, oral calcium used as phosphate binder in association with phosphate restriction and correction of possible vitamin D depletion and acidosis is usually efficace to control hyperparathyroïdism without 1 alpha OH vitamin D3. This is not the case in the child to whom protein and phosphate restriction should not be prescribed because of its incompatibility with the Recommended Diet Allowance. Fortunately the high remodeling rate of his growing bones, decreases the risk of hypercalcemia due to the combination of CaCO3 and 1 alpha OH vitamin D3.

Progress in bone densitometry, particularly biphotonic absoptiometry, has made it possible to better identify the effects of endocrinopathies on bone. Both cortical and trabecular bone structures can be evaluated quantitatively and topographically revealing important information on the pathophysiology of bone loss. Sex hormones play a major role in the regulation of bone mineralization and hypogonadism, whatever the origin, can lead to deleterious effects. Bone loss is known to be significative in high performance female athletes with amenorrhoea; long-term consequences are not yet determined, but stress fractures have been reported in up to 50%. Other hypogonadisms leading to bone demineralization include anorexia nervosa, chronic intake of gonadotrophin releasing hormone analogues and anti-oestrogens, and hyperprolactinism. Hyperthyroidism leads to a negative calcium balance and demineralization with remodelling, predominantly in cortical bone. In hypothyroid states a 10% bone loss is observed in vertebrae. In both cases, bone densitometry should be performed in order to evaluate the effect of treatment. The deleterious effect of spontaneous or iatrogenic hypercortisism is well known, leading to spontaneous wedge fractures of the vertebrae due to predominating trabecular bone loss. The mechanism of action of corticosteroids on bone metabolism is complex, but the major effect is an inhibition of osteoblast maturation. Recovery may be possible, but no large long-term series have yet been reported. Hyperparathyroidism and acromegaly also affect bone mineralization. The information provided by bone densitometry is essential to properly manage patients with endocrinopathies affecting bone mineralization.

The aim of the study was fa evaluate in Wistar rats the promoting effect of poiyunsaturated (n-6)or saturated (végétaline) fats (24%) in colon carcinogenesis and the influence of supplemental calcium(1.5%) in this process. NMU was intrarectally instillated to induce colon carcinogenesis. Three differentcalcium salts (carbonate, lactate, and gluconate) were tested. Colon cancer incidence was higher in rats fed saturated fats than in those consuming unsaturated ones.The calcium supplementalion exhibits a protective effect depending on the chemical form used.Calcium lactate provide better protection than carbonate or gluconate.From the parameters those were used to follow carcinogenesis, resulls indicate that calcium salt acts through several ways, luminal and systemic. It chelates fatty acids and bile acids in the lumen and modulates the microbial transformations of cholesterol and bile acids, thus reflecting a modification of the intestinal microflora. The calcium balance suggests that the proteclive effect of calcium lactate is also efficient in reducing the cellular proliferation.Laminin P1 is proposed as a possible tumoral marker. Its serum levels are associated with colon tumorigenesis.; Ce travail analyse chez les rats wistar, le rôle promoteur des régimes hyper lipidiques polyinsaturés (n6) et satures (vegetaline) ainsi que l'influence de la supplémentassions calcique (1.5%) sous forme carbonate, lactate ou gluconate vis-à-vis de la carcinogenèse colique induite par la NMU. Les lipides saturés, en présence de la NMU, sont des promoteurs potentiels de la carcinogenèse colique. La protection vis-à-vis de la carcinogenèse colique dépend de la forme chimique du sel de calcium. Le lactate de calcium semble avoir plus d'effets relativement au carbonate et gluconate de calcium. Cet effet protecteur du calcium se manifeste sur plusieurs niveaux (luminal et systémique) et à différentes étapes de la carcinogenèse (prolifération, promotion et progression). Le calcium agit principalement par la chélation des acides biliaires et surtout des acides gras et à travers la modulation des transformations bactériennes du cholestérol et de ses dérivés. Les bilans calciques suggèrent que l'effet du lactate de calcium est également systémique à travers la diminution de la prolifération cellulaire. La laminine p1 est proposée comme un marqueur tumoral. Les taux sériques de cette protéine sont associés à la tumorigenese colique.

The aim of the study was fa evaluate in Wistar rats the promoting effect of poiyunsaturated (n-6)or saturated (végétaline) fats (24%) in colon carcinogenesis and the influence of supplemental calcium(1.5%) in this process. NMU was intrarectally instillated to induce colon carcinogenesis. Three differentcalcium salts (carbonate, lactate, and gluconate) were tested. Colon cancer incidence was higher in rats fed saturated fats than in those consuming unsaturated ones.The calcium supplementalion exhibits a protective effect depending on the chemical form used.Calcium lactate provide better protection than carbonate or gluconate.From the parameters those were used to follow carcinogenesis, resulls indicate that calcium salt acts through several ways, luminal and systemic. It chelates fatty acids and bile acids in the lumen and modulates the microbial transformations of cholesterol and bile acids, thus reflecting a modification of the intestinal microflora. The calcium balance suggests that the proteclive effect of calcium lactate is also efficient in reducing the cellular proliferation.Laminin P1 is proposed as a possible tumoral marker. Its serum levels are associated with colon tumorigenesis.; Ce travail analyse chez les rats wistar, le rôle promoteur des régimes hyper lipidiques polyinsaturés (n6) et satures (vegetaline) ainsi que l'influence de la supplémentassions calcique (1.5%) sous forme carbonate, lactate ou gluconate vis-à-vis de la carcinogenèse colique induite par la NMU. Les lipides saturés, en présence de la NMU, sont des promoteurs potentiels de la carcinogenèse colique. La protection vis-à-vis de la carcinogenèse colique dépend de la forme chimique du sel de calcium. Le lactate de calcium semble avoir plus d'effets relativement au carbonate et gluconate de calcium. Cet effet protecteur du calcium se manifeste sur plusieurs niveaux (luminal et systémique) et à différentes étapes de la carcinogenèse (prolifération, promotion et progression). Le calcium agit principalement par la chélation des acides biliaires et surtout des acides gras et à travers la modulation des transformations bactériennes du cholestérol et de ses dérivés. Les bilans calciques suggèrent que l'effet du lactate de calcium est également systémique à travers la diminution de la prolifération cellulaire. La laminine p1 est proposée comme un marqueur tumoral. Les taux sériques de cette protéine sont associés à la tumorigenese colique.

Long-term corticosteroid therapy is the most frequent and most severe cause of iatrogenic osteoporosis. Hypocalcaemia, subsequent to the induced negative calcium balance, may lead to secondary hyperparathyroidism. Corticosteroids also affect bone itself, probably by disrupting the production of growth factors. Bone resorption increases and bone formation decreases leading to a reduction in total bone mass. The relative immobilization resulting from the corticoid-induced myopathy or the underlying disease may accelerate the process. On the average, after one year of treatment, 5% of the bone mass is lost, and loss may reach as much as 10 to 30% at certain sites. Nearly 40% of all subjects on long-term corticosteroids suffer fractures. Other iatrogenic causes include anticonvulants which perturb phosphocalcium metabolism, 1-thyroxin which leads to bone loss when administered for hormone substitution, gonadotropin-releasing hormone antagonists which inhibit the hypophyseal-ovarian axis, tamoxifen (used in the treatment of breast cancer) which has an oestrogen-like effect, and other circumstances such as chemotherapy and long-term heparin. The gravity of iatrogenic osteroporosis thus requires preventive measures. Calcium and vitamin D supplements can compensate for impaired intestinal absorption of calcium but have no effect on bone density. One-alpha hydroxyl derivatives have been suggested but their effect remains controversial. Calcitriol can prevent bone loss in the lumbar vertebrae but hypercalcaemia occurs in one-fourth of the cases, limiting its use. Recent reports have shown that anti-oestroclastic agents may be useful. Nandrolone decaonate would have a favourable effect on bone loss but also causes virilization. In patent osteoporosis, fluorine can be combined with calcium resulting in increased lumbar bone density. Calcitonin and calcium can also be combined to induce a rise in bone density. The long-term effects of these treatments in terms of reduced fracture risk remain to be determined. A better understanding of the adverse effects of the different classes of corticosteroids is essential for optimal treatment. In cases requiring long-term therapy implicating the risk of iatrogenic osteoporosis, bone density quantitation can be a valuable means of evaluating bone loss, and of adapting preventive or corrective measures.