Biomedical subjects

L Miravet

Publications and source records attributed to L Miravet.

At least 19 recordsLinked to original sources

PubMed1992

Evidence for efficacy of drugs affecting bone metabolism in preventing hip fracture.

OBJECTIVE: To examine the effects of taking drugs affecting bone metabolism on the risk of hip fracture in women aged over 50 years. DESIGN: Retrospective, population based, case-control study by questionnaire. SETTING: 14 centres in six countries in southern Europe. SUBJECTS: 2086 women with hip fracture and 3532 control women matched for age. MAIN OUTCOME MEASURES: Number of drugs affecting bone metabolism taken and length taken for. RESULTS: Women taking drugs affecting bone metabolism had a significantly decreased risk of hip fracture. After adjustment for differences in other risk factors, the relative risk of hip fractures was 0.55 (95% confidence interval 0.31 to 0.85) in women taking oestrogens, 0.75 (0.60 to 0.94) in those taking calcium, and 0.69 (0.51 to 0.92) in those taking calcitonin. The fall in risk was not significant for anabolic steroids (0.6 (0.29 to 1.22)). Neither vitamin D nor fluorides were associated with a significant decrease in the risk of hip fracture. The effect on hip fracture risk increased significantly with increasing duration of exposure (risk ratio 0.8 (0.61 to 1.05) for less than median exposure v 0.66 (0.5 to 0.88) for greater than median exposure). Drugs were equally effective in older and younger women, with the exception of oestrogen. CONCLUSIONS: Oestrogen, calcium, and calcitonins significantly decrease the risk of hip fracture. Short term intervention late in the natural course of osteoporosis may have significant effects on the incidence of hip fracture.

Aged↗

PubMed1992

Effect of fluoride on bone and bone cells in ovariectomized rats.

To evaluate whether treatment with a mitogenic agent may increase bone formation and bone mass in osteopenia induced by estrogen deficiency, we determined the effect of oral fluoride treatment on bone and bone cells in ovariectomized rats. Sodium fluoride (NaF) was administered to 3-month-old ovariectomized rats 1 day after ovariectomy (OVX) for 1, 3, and 6 months. NaF was given in drinking water at the dose of 1 mg/kg body weight per day. Fluoride administration led to a partial prevention of the bone loss induced by OVX as shown by histologic analysis of tibial metaphysis and by evaluation of femoral calcium content. These beneficial effects of fluoride were more striking at early time points (1 and 3 months postovariectomy) than after 6 months of treatment. The increase in trabecular bone volume in OVX rats treated with fluoride was associated with a rise in the osteoblast surface, which was increased by 60, 72, and 235% at 1, 3, and 6 months postovariectomy compared to untreated OVX rats. In OVX rats and in sham-operated rats plasma osteocalcin was increased in correlation with the osteoblast surface. However, these two parameters were not correlated in OVX rats treated with fluoride. The heat-labile bone-specific alkaline phosphatase in plasma was decreased in OVX rats treated with fluoride compared to OVX rats, suggesting that both the number and the activity of osteoblasts were affected by NaF treatment. To examine the effect of fluoride on the osteocalcin production and the proliferative capacity of bone cells, osteoblastic cells were isolated by collagenase digestion from the bone surface of tibia in treated and untreated OVX rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

PubMed1992

Dynamics of circulating osteocalcin in rats during growth and under experimental conditions.

Osteocalcin is the most abundant non-collagenous protein produced in the process of bone formation. A specific radioimmunoassay has been developed using a rabbit antiserum raised against osteocalcin extracted from rat bone. The sensitivity of the assay was tested in male and female rats under different experimental conditions: ovariectomy led to a mild increase in circulating osteocalcin (70.6 +/- 6.9 vs 51.6 +/- 6.3 ng/ml; p < 0.05) and deprivation of dietary calcium elevated plasma levels further (119 +/- 6.3 ng/ml; p < 0.01). As expected, pharmacological enhancement of bone turnover with calcitriol produced a significant increase in plasma osteocalcin (296 +/- 24.1 vs 89.5 +/- 5.1 ng/ml; p < 0.01), whereas prednisolone, a steroidal compound known to inhibit osteoid mineralization, significantly reduced circulating concentrations of this protein (70 +/- 7.4 vs 100 +/- 6.3 ng/ml; p < 0.05). Plasma kinetics recorded in female rats between birth and the 100th week revealed a highly significant (p < 0.001) elevation peaking at the third week (231 +/- 70.6 ng/ml) and slowly declining to reach values measured at birth (41.3 +/- 9.2 ng/ml) at the 16th week (47 +/- 4.6 ng/ml). Subsequently, a small but significant (p < 0.05) decline towards senescence was recorded. The osteocalcin surge preceded the period of rapid growth (weeks 3 to 11) estimated by vertebral length progression, showing a tendency to stabilize as growth spurt slowed down. A moderate but significant (p < 0.01) increment was observed after mating (87.8 +/- 5.1 vs 69.5 +/- 4.0 ng/ml). Although plasma osteocalcin remained stable during lactation, average levels were elevated in comparison with age-matched non-pregnant controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1991

Calcemic response to magnesium or 1-alpha-hydroxycholecalciferol treatment in intestinal hypomagnesemia.

The mechanism of hypocalcemia was assessed prospectively in 10 gastroenterological hypomagnesemic patients. Baseline serum magnesium was 0.9 +/- 0.1 mg/dl and calcium, 7.2 +/- 0.4 md/dl. Plasma 25-hydroxyvitamin D (25 (OH)D) was low in 5 patients and normal in the others. Plasma parathormone (PTH) and urinary cyclic AMP (ur. cAMP), although twofold above normal values, were inappropriately low and increased sharply after a magnesium bolus injection. There was no renal resistance to PTH as ur. cAMP increased after i.v. bovine PTH bolus injection. Subsequently, patients were randomly divided into 2 groups, each including patients with low or normal levels of 25 (OH)D, receiving either MgCl2 (group I) or 1 microgram/d of 1-alpha (OH)D (group II) for one week. Although magnesium status remained low in group II patients, increase in plasma calcium was identical in both groups. Serum calcium levels in patients receiving combined 1-alpha (OH)D and MgCl2 during a second week of treatment returned to normal. In the 4 tested patients, plasma 1,25 (OH)2D levels were low before, but also after correction of hypomagnesemia, suggesting that low level of 1,25 (OH)2D might not be due to hypomagnesemia. Therefore, treatment with low dosage of 1-alpha (OH)2D associated with magnesium chloride repletion can be recommended to restore normal calcium homeostasis in patients with intestinal hypomagnesemia.

Adult↗

PubMed1991

Agenesis of the right pulmonary artery in a young asymptomatic girl.

We report the case of a 13 yr old, asymptomatic girl with agenesis of the right pulmonary artery. In the context of a tuberculosis survey in her school, an X-ray examination disclosed a decreased volume of the right lung. Ventilation and perfusion scans and digital substraction angiography established the diagnosis.

Adolescent↗

PubMed1990

Stress fractures of the lower limbs in osteoporotic patients treated with fluoride.

We report clinical and bone morphometric findings in 18 osteoporotic patients who experienced stress fractures during fluoride therapy. Patients were treated with either sodium fluoride (n = 15), or sodium monofluorophosphate (n = 3). Oral calcium supplementation was given in 11 patients, and vitamin D in 13. Stress fractures occurred after 17.1 +/- 10.3 months of therapy (range: 5-41 months). Atraumatic sudden pain in a lower limb bone extremity, normal initial roentgenogram, high 99technetium uptake on early bone scan, and a 3 to 4 week delay in linear bone condensation area at the same site were characteristics of stress fracture. The most frequent sites were the tibial metaphysis (n = 13), femoral neck (n = 10), and calcaneus (n = 4). Biochemical data showed increased plasma alkaline phosphatase levels in 11 patients, and mild renal failure in 2. Bone histomorphometry was performed on an iliac crest specimen in 10 patients at the time of the stress fracture. Trabecular bone volume was normal, and formation parameters were increased. Features of osteomalacia were encountered in only 2 patients with decreased renal function. Trabecular resorption was increased, as assessed by the osteoclastic surface (1.01 +/- 1.15% bone surface), and the number of osteoclasts (0.44 +/- 0.49 per mm2 bone section). The clinical course was favorable in all patients who stopped fluoride, although 5 patients who continued the treatment had either completion of femoral neck stress fractures to hip fractures (n = 2), or recurrent stress fractures (n = 2), or both (n = 1). Fluoride appears to be a key factor in the pathogenesis of stress fractures, and may be associated with increased trabecular resorption in some treated patients.

Aged↗

PubMed1990

Effect of calcitonin administration on young pig trabecular bone remodeling.

Ten-week-old pigs were treated with 4 different treatment schedules of porcine calcitonin for 2 months. Groups C1 and C4 received continuous treatment: C1 had daily IM injections (4 IU/kg/BW (body weight) each injection), and C4 was infused with a minipump implanted subcutaneously delivering 4 IU/kg/BW/day. Groups C2 and C3 received intermittent calcitonin treatment (each injection 4 IU/kg/BW): C2 was given 1 out of every four days, C3 was injected 5 consecutive days out of 20 days. The total dosage received in C1 versus C4 and C2 versus C3 were the same. Results were evaluated by histomorphometry after double tetracycline labeling on iliac trabecular bone. Resorption surfaces were decreased in groups C2, C3 and C4, but bone volume, osteoclast surfaces, and interstitial bone thickness were not modified in any group receiving calcitonin. Osteoblast and mineralizing surfaces were increased in group C2, C3 and C4. Plasma 1,25-dihydroxyvitamin D concentration and bone formation rate were increased in groups C2 and C4. Plasma immunoreactive parathyroid hormone levels and parathyroid weights were not increased in any treated groups. In conclusion, 2-month calcitonin treatment did not decrease the amount of bone resorbed in growing pigs. Continuous calcitonin infusion and intermittent calcitonin administration induced an increase in the extent of active bone formation which might be in part dependent on an increased production of 1,25 dihydroxyvitamin D.

Animals↗

PubMed1990

Comparative effects of a novel vitamin D analogue MC-903 and 1,25-dihydroxyvitamin D3 on alkaline phosphatase activity, osteocalcin and DNA synthesis by human osteoblastic cells in culture.

MC-903 is a novel vitamin D analogue which has been shown to promote epidermal cell differentiation but is 100 times less active than 1,25 dihydroxyvitamin D3 (1,25(OH)2D) in causing hypercalcemia. In order to determine the activity of this compound on bone cells, we have compared the effects of MC-903 and 1,25 dihydroxyvitamin D3 (1,25(OH)2D) on parameters of cell proliferation and differentiation in cultured normal human osteoblastic cells derived by migration from trabecular bone fragments. Dose response curves showed that MC-903 was 10 to 100 times less effective than 1,25(OH)2D in stimulating the synthesis of the osteoblast specific protein osteocalcin by human bone cells depending on the basal osteocalcin production. In cells showing high basal osteocalcin synthesis, 1,25(OH)2D (10(-8) M) was 2- to 3-fold more potent than MC-903 (10(-8) M) in inducing osteocalcin from 48 to 96 h of treatment. The greater activity of 1,25(OH)2D over MC-903 was observed in human bone cell cultures with elevated basal osteocalcin levels, indicating that the response to 1,25(OH)2D but not to MC-903 was amplified in cells with the higher osteoblastic characteristics. The effects of MC-903 and 1,25(OH)2D on alkaline phosphatase activity were not markedly different. Transforming Growth Factor-beta (TGF beta) (0.5 ng/mL, 48 h) was found to completely suppress the osteocalcin synthesis induced by 1,25(OH)2D (10(-8) and 10(-9) M), whereas the MC-903-induced osteocalcin synthesis was not affected, suggesting a negative interaction between TGF beta and 1,25(OH)2D but not MC-903 on osteocalcin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

PubMed1989

[Value of bone fluoride determination in osteoporotic patients treated with sodium fluoride].

In order to find out whether the response of osteoporosis to sodium fluoride treatment or complications arising from this treatment are related to the retention of fluoride in bones, we measured bone fluoride concentrations in 30 patients with primary osteoporosis who had been treated with sodium fluoride for 1 to 8 years. We found a significant correlation (r = 0.74, P less than 0.001) between bone fluoride concentration and total amount of fluoride ingested. However, with any given amount of sodium fluoride, the bone fluoride concentration could vary by up to three times from a patient to another. There was a significant correlation between bone fluoride concentration and trabecular bone volume on the hand (r = 0.54, P less than 0.001) and thickness of osteoid borders measured on the same biopsy specimen on the other hand (r = 0.45, P less than 0.001). Five patients developed lower limb bone fissures after 11 to 18 months of sodium fluoride treatment, but their bone fluoride concentration was not significantly different from that of the 25 patients who had no fracture. These data suggest a relationship between the degree of stimulation of bone formation by fluoride and the bone concentration of that substance; however, peripheral fractures are not dependent on bone fluoride concentration.

Adult↗

PubMed1989

[Amino-hydroxy-propylidene biphosphonate in the treatment of Paget's disease resistant to calcitonin and/or etidronate].

18 patients with Paget's disease resistant to calcitonin and/or to EHDP (ethane-hydroxy bisphosphonate) were treated with APD (disodium amino-hydroxypropylidene-bisphosphonate). The efficacy of the product was judged by the decrease in serum alkaline phosphatases and of hydroxyproline in the 24-hour urine specimen. The treatment lasted for a maximum of 6 months. Administration of APD was stopped before six months if he hydroxyproline content in the urine returned to normal (except in the case of four patients where the early interruption of treatment was due to lack of supplies). Of the 14 patients who followed the regular course of treatment, the urine hydroxyproline became normal between the first and the sixth month of treatment in 11 patients: at the start, all had a 24-hour urine hydroxyproline content equal to or less than 2.1 mmol/l 24 h (275 mg/24 h). The baseline 24-hour urine hydroxyproline in the remaining three patients was higher (3.55; 2.30; 3.28 mmol/24 h), but the level was reduced by 50% after 6 months of treatment. Alkaline phosphatases were reduced in the same proportions but the decrease occurred at a slightly later date. The residual activity was evaluated in 9 subjects who had not received any treatment for one year: in 8 out of the 9 patients the parameters used for measuring bone activity had not appreciably altered. Treatment with APD was restarted in 4 patients after a period of 12 to 36 months without therapy, and its efficacy was found to be comparable to that of the drug's first use. In all, APD demonstrated remarkable efficacy in pagetic patients resistant to both calcitonin and/or EHDP.

Adult↗

PubMed1989

Cyclosporin A induces in vivo inhibition of resorption and stimulation of formation in rat bone.

We investigated a possible "in vivo" effect of cyclosporin A, an immunosuppressive agent, on normal rat bone remodeling. At an oral daily dose of 7 mg/kg for 14 days, the blood level of cyclosporin A was in the usual effective range and no change in renal function or magnesium metabolism was observed. Treated rats had decreased bone resorption: urinary hydroxyproline, plasma acid phosphatase, and the number of osteoclasts in caudal vertebrae were significantly reduced. By contrast, bone formation assessed by dynamic histomorphometry after double tetracycline labeling was increased. No modification of calciotropic hormones (vitamin D metabolites and parathyroid hormone as assessed by urinary cyclic AMP) was observed at the end of the treatment. These results suggest that in vivo cyclosporin A treatment induces bone remodeling modifications related to either a direct or a lymphokine-mediated effect on bone cells.

Acid Phosphatase↗

PubMed1989

Decreased bone formation in osteoporotic patients compared with age-matched controls.

In order to study trabecular bone remodeling in postmenopausal osteoporosis we compared bone biopsies of 44 osteoporotic women aged 50-70 to those of 23 nonosteoporotic women, matched for age, who had a bone biopsy during anesthesia for knee arthritis. Trabecular bone volume, mean wall thickness, osteoblastic surfaces, labeled surfaces, and bone formation rate were decreased in osteoporotic women compared with control women. The osteoclast number and the osteoclastic surfaces were the same in the two groups. The normal distribution of the histomorphometric static parameters in osteoporotic patients did not allow the separation of subgroups. These data indicate that decreased bone formations is a major contributing factor leading to trabecular bone loss in postmenopausal osteoporosis.

Age Factors↗

PubMed1988

Osteocalcin and bone morphometric parameters in adults without bone disease.

Serum bone Gla-protein (s-BGP or osteocalcin) and other serum biochemical parameters were measured in 19 subjects (8 women and 11 men, aged 20-82 years) without any bone disease. Each subject simultaneously underwent an iliac crest biopsy; tetracycline double-labeling was performed in 11 subjects, allowing correlations between s-BGP and bone histomorphometric parameters. s-BGP was significantly correlated with static bone parameters: trabecular bone volume (r = 0.74; P less than 0.001), osteoid surfaces (r = 0.69; P less than 0.001), osteoblastic surfaces (r = 0.68; P less than 0.002); dynamic bone formation parameters: total labeled surfaces (r = 0.72; P less than 0.01); and the bone formation rate (r = 0.69; P less than 0.01). We conclude that s-BGP is a valuable marker for evaluating bone formation in healthy adult subjects.

Adult↗

PubMed1988

[Primary hyperparathyroidism seen in rheumatology. Clinical symptoms and the relation between bone histologic signs and biological parameters].

We report the clinical and biological picture of 34 primary hyperparathyroidism (PHT) cases, diagnosed in rheumatology. It concerned 25 women and 9 men, aged 61 + 11 years. The PHT was often asymptomatic (47 p. cent of cases) at the time of diagnosis. The clinical manifestations were dominated by asthenia (50 p. cent) and renal lithiasis (47 p. cent). We found a chondrocalcinosis in 29 p. cent of patients. No patient presented any bony manifestations of cystic osteitis; 7 out of 34 patients (including 6 women between 57 and 74 years) presented vertebral compression. The mean calcemia was 117 +/- 9 mg/l. There were no hypercalcemic attack. The dosage of PTH and cyclic AMP were elevated in 29 out of 32 and 28 out of 31 patients respectively. In all patients, the level of either of these two tests was increased. The chloremia/phosphoremia ratio was also extremely predictive of HBP, since it was increased, exceeding 3.3 in 33 out of 34 patients. The 25-hydroxyvitamin D levels (25 (OH) D) were normal. The levels of 1,25 (OH) 2D were markedly spread (37 +/- 16 pg/ml) and not significantly different from the reference group. Patients with lithiasis did not present a higher level of 1,25 (OH) 2D. A bone histomorphometry carried out in 15 patients showed a bone trabecular volume similar to that of the reference with the same age. The osteoclastic resorption was increased in all cases and was not correlated with the PTH level, but was significantly correlated with the level of 1,25 (OH) 2D (r = 0.79 p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1988

The prevalence of chondrocalcinosis in the human knee joint. An autopsy survey.

The prevalence of pathological calcifications in the menisci and articular cartilage of both knees was investigated macroscopically and radiologically in 130 consecutive autopsies. The mean age of the subjects was 72 +/- 13 years. Only 8 subjects were less than 50 years old. All had been admitted to hospital and no patient had a history of joint disorders. Half of the patients were male. Calcifications were found in 27 (20.7%) cases, all over 60 years of age. There were 15.4% males and 26.1% females affected. The incidence of intraarticular calcifications in females increased from 11.1-37.5% and in males from 20-29.4% for the 60-69 year age group and the over 80-year age group, respectively. One third of affected cases had only meniscal and 2/3 had both meniscal and chondral calcifications. Isolated meniscal calcifications were found more often in 1 and mixed meniscal and chondral calcifications were found in both knees. Severe destructive articular cartilage lesions were observed significantly more often in joints with intraarticular calcifications than in joints of age matched subjects without calcifications. Joints with calcifications showed little evidence of synovial inflammation. Similarly, no specific relationship was found between the presence of crystal and amyloid deposits in the knees examined.

Aged↗

PubMed1987

Different schedules of administration of (3 amino-1-hydroxypropylidene)-1, 1 bisphosphonate induce different changes in pig bone remodeling.

Intermittent administration of antiosteoclastic agents has been proposed in order to increase trabecular bone volume (TBV). We evaluated the effect of two different intermittent schedules of administration of (3 amino-1-hydroxypropylidene)-1, 1 bisphosphonate (AHPrBP) on pig bone remodeling for a period of 60 days. AHPrBP (1.6 mumol/kg/injection) was given subcutaneously daily (group A1), or 5 consecutive days out of 21 days (group A2), or 1 out of every fourth day (group A3). Compared to control animals, group A1 significantly increased trabecular bone volume (TBV) (+62%) with a marked decrease in bone resorption assessed by interstitial bone thickness. Bone formation assessed by mean wall thickness (MWT) was also decreased due to a decrease in the number and activity of osteoblasts. There was not a delay in the coupling mechanism as assessed by the reversal surfaces. The two groups receiving intermittent schedules had markedly different results. Group A2 had very similar changes to group A1 despite receiving four time less drug. Compared to group A1 and A2, group A3 had smaller decrease in resorption and higher bone formation rate with identical MWT. These differences between group A2 and A3 were associated with similar levels of parathyroid hormone and vitamin D metabolites. Different bone concentrations induced by the two different schedules of AHPrBP may explain the greater effect on bone resorption and osteoblast recruitment in group A2 and thus a milder effect of the AHPrBP administration once every fourth day.

Animals↗

PubMed1987

Bone histological heterogeneity in postmenopausal osteoporosis: a sequential histomorphometric study.

We studied sequential bone biopsies performed at 6 to 24 month intervals from 14 untreated osteoporotic women (64 +/- 7). Subgroups were defined, respectively, by increased osteoclastic resorption surfaces and decreased osteoblastic surfaces +/- 2 S.D. Normal values were obtained from bone biopsy of 23 normal women (61 +/- 8). When patients were divided into subgroups according to the above criteria the first biopsy showed that 3 out of the 14 patients had high resorption surfaces and 6 had low osteoblastic surfaces. Eight patients spontaneously changed during the study. In 2 patients there was a change in resorption surfaces, in 3 in osteoblastic surfaces and in 3 a change in both osteoblastic and resorption surfaces was observed. Considering the first or second bone biopsy results the patient variance was higher than the control subject's variance; however the variance between the first and second bone biopsy of one patient was not different from the variance inside the group of patients. The average intraindividual variation of the parameters on sequential biopsies was of the same order as the one we previously observed on simultaneous bone biopsies of normal and hemodialyzed patients. We concluded that if osteoporosis is a heterogeneous disorder, subgroups cannot be definitively defined on the basis of cellular parameters of bone remodelling assessed on bone biopsies.

Aged↗

PubMed1987

Lack of biological activity of vitamin D3-3 beta sulfate during lactation in vitamin D-deficient rats.

Sulfoconjugated vitamin D has been claimed to have an important antirachitic activity and to be present at higher amounts than free vitamin D in maternal milk. We have previously shown that vitamin D3-3 beta sulfate (SD3) administration has little effect on calcium and bone metabolism during pregnancy in rats. In the present work, we have compared the biological activity of free vitamin D3 (D3) and SD3 during the lactation period. After delivery, D-depleted (-D) female rats were orally treated with D3 or SD3 (1,300 pmoles/every two days) during 20 days of lactation. Vitamin D status was determined before, during and at the end of the treatment for mother rats and at days 1 and 20 of life in suckling pups. Both mothers and pups were sacrificed at day 20 of lactation and subjected to hormonal and mineral determinations and to histomorphometric analysis of bone metabolism. After 12 days of SD3 treatment, mother rats showed a slight but significant elevation in plasma concentrations of calcium phosphorus and vitamin D metabolites. This effect was reversed at the end of lactation; at this time most maternal plasma parameters did not differ from those observed in -D non-treated mothers. By contrast, 20 days of D3 administration in mothers normalized plasma biochemical parameters. These results were confirmed by analysis of both static and dynamic parameters of bone formation. Maternal SD3 treatment did not improve either plasma biochemical or histological parameters of bone formation and resorption in suckling pups which remained comparable to that of D-deficient pups; by contrast, pups from D3-treated mothers normalized most biochemical plasma parameters although bone metabolism remained abnormal. In conclusion, the biological activity of SD3 on bone and mineral metabolism during lactation in rats is as low as in the nonreproductive stages.

Animals↗