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Biomedical subjects

R Deroisy

Publications and source records attributed to R Deroisy.

At least 37 records · Page 2Linked to original sources

Long-term (3 years) prevention of trabecular postmenopausal bone loss with low-dose intermittent nasal salmon calcitonin.

The long-term effect of intermittent low-dose nasal salmon calcitonin on trabecular early postmenopausal bone loss was assessed as follow-up to a previously published study. Randomized controlled group comparison was made of 287 healthy women with 6-36 months of natural menopause and no treatment interfering with calcium metabolism at an outpatient clinic for research in bone and cartilage metabolism. The 287 women were randomly allocated to 3 years of treatment with either 500 mg/day, 5 days/week of calcium or the same amount of calcium plus 50 IU/day, 5 days per week of nasal salmon calcitonin. A total of 186 women complied with the study protocol throughout. The main outcome measures were bone mineral density of the lumbar spine (DPA) and biochemical parameters reflecting bone turnover (serum alkaline phosphatases, urinary calcium/creatinine, and hydroxyproline/creatinine ratio). The average changes in bone mineral density after 36 months showed a positive (p < 0.05) outcome (1.8 +/- 5.7%; mean +/- SD) in the group treated with salmon calcitonin and calcium and a significant (p < 0.01) loss (-5.8 +/- 4.8%) in patients receiving calcium alone. The difference between the evolution of the two groups was significantly (p < 0.01) different after 6 months of treatment and remained so until the end of the study. No significant changes were recorded in biochemical parameters reflecting bone turnover. As previously shown during a 1 year follow-up, nasal salmon calcitonin given at low dose and intermittently, in association with calcium, can counteract trabecular postmenopausal bone loss.

Administration, Intranasal↗

A 5-year controlled randomized study of prevention of postmenopausal trabecular bone loss with nasal salmon calcitonin and calcium.

The aim of this paper was to evaluate the long-term (5 years) efficacy of nasal salmon calcitonin in prevention of trabecular postmenopausal bone loss, which was a follow-up of a previously published study (3 years); a randomized, controlled group comparison. One hundred healthy postmenopausal women were randomly chosen from those (186) having completed the 3 year protocol. The 100 women were allocated to an additional 2 year period (total of 5 years) of treatment with either 500 mg d-1, 5 days week-1 of calcium or the same amount of calcium plus 50 IU d-1, 5 days per week of nasal salmon calcitonin, 87 (87%) women complied with the protocol throughout. The main outcome measures were the bone mineral density of the lumbar spine (1-BMD) (DPA) and biochemical parameters reflecting bone turnover (serum alkaline phosphatases, urinary calcium/creatinine and hydroxyproline/creatinine ratios). The women receiving calcium alone presented a significant decrease in 1-BMD after 6 months [-1.6 (0.5)%] [mean(SEM)] (P < 0.01) and this decrease remained significant after 36 months [-6.1(0.8)%] (P < 0.01) and until the end of the trial [-6.6(1.0)% at t60] (P < 0.01). In women receiving calcium and calcitonin, 1-BMD significantly increased after 36 months [+2(0.7%] (P < 0.01) and 42 months [+2.5(0.7)%] (P < 0.01 and was unchanged at the other times of investigation [+1.1 (1.1)% at t60] (NS). The evolution of BMD in the two groups was highly significantly different (P < 0.001) since the sixth month of the study and remained so until the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Effect of transdermal 17 beta-estradiol and oral conjugated equine estrogens on biochemical parameters of bone resorption in natural menopause.

OBJECTIVE: To evaluate and compare the effects or oral and transdermal estrogen replacement therapy on biochemical markers of bone resorption in early postmenopausal women. DESIGN: Controlled, randomized group comparison. SETTING: Outpatient clinic for menopausal women and research into osteoporosis. SUBJECTS: Sixty healthy women menopausal for less than 5 years and who had never received any medications interfering with bone metabolism. INTERVENTIONS: The 60 women were randomly allocated to 3 months therapy with either oral conjugated estrogens (0.625 mg/day) (n = 28) or transdermal estradiol (50 micrograms/day) (n = 32) in cyclical combination with medroxyprogesterone acetate (5 mg/day). MAIN OUTCOME MEASURES: Traditional (urinary calcium/creatinine and hydroxyproline/creatinine) and the new specific (urinary pyridinoline/creatinine and deoxypyridinoline/creatinine) markers of bone resorption were determined before and after 3 months of treatment. RESULTS: In both groups, circulating levels of estrone and estradiol were significantly (P < 0.001) increased during treatment. In women treated with oral conjugated equine estrogens, urinary calcium/creatinine and hydroxyproline/creatinine ratios were significantly (P < 0.05) reduced. Pyridinoline/creatinine ratio fell from 69.1 (4) [mean (SEM)] to 50 (4) mumol/mumol (P < 0.01) and deoxypyridinoline/creatinine ratio fell from 10.8 (1) [mean (SEM)] to 8.3 (0.8) mumol/mumol (P < 0.01). In the group treated with transdermal estradiol, urinary hydroxyproline/creatinine ratio was significantly (P < 0.05) reduced. Pyridinoline/creatinine ratio fell from 66.3 (4) [mean (SEM)] to 46.2 (3) mumol/mumol (P < 0.01) and deoxypyridinoline/creatinine ratio fell from 11.5 (1.5) [mean (SEM)] to 7.7 (0.6) mumol/mumol (P < 0.01). There were no differences between the evolution of the biochemical variables in the two groups. CONCLUSION: These results suggest that oral conjugated equine estrogens and transdermal estradiol, in the given doses, are equally effective in reducing postmenopausal bone resorption.

Administration, Cutaneous↗

Prevention of osteoporosis with nasal salmon calcitonin: effect of anti-salmon calcitonin antibody formation.

The amino acid sequence of salmon calcitonin (SCT) differs considerably from that of the human hormone and specific antibodies (Ab) develop in a significant proportion of patients after parenteral or nasal administration of SCT. Controversy remains regarding the functional importance of these Ab. We report on the development of specific anti-SCT Ab in a population of postmenopausal women receiving nasal SCT for prevention of postmenopausal bone loss, and compare the effects of nasal SCT in women with or without Ab. Thirty-nine per cent of women developed Ab after 6 months of treatment with SCT, 52% after 12 months, and 61% after 18 and 24 months. After 24 months the AB titre was 3.47-17.7 x 10(-9) M/l (mean +/- SD: 13.3 +/- 3.1 x 10(-9) M/l). No significant differences appeared between the changes in lumbar bone mineral density (BMD) measured in the whole population (n = 44) (mean +/- SD: +1.06 +/- 3.9%), the patients without Ab (n = 17) (+0.05 +/- 3.7%) or in those with Ab (n = 27) (+1.7 +/- 4.6%). During the same period, a control population randomly assigned to a 500 mg/day calcium intake showed a significant loss of lumbar BMD (-4.57 +/- 4.9%) (p < 0.01). In conclusion, in healthy postmenopausal women nasal SCT seems to maintain the same preventive effect against bone loss whether or not Ab are present.

Administration, Intranasal↗

Acute biochemical variations induced by four different calcium salts in healthy male volunteers.

Calcium (Ca) supplements have positive effects in growing children, reduce bone loss in late-postmenopausal women with a low calcium diet and, in association with vitamin D3 supplements, may reduce non-vertebral fracture rates in elderly women. However, for many formulated pharmaceutical products their relative beneficial effects have not been conclusively established. We have compared the acute (6 h) metabolic responses following oral administration of two preparations of calcium gluconolactate and carbonate (CG and CG'), tricalcium phosphate (TCP) and calcium citrate (CC), given on separate occasions in each of 10 healthy young male volunteers. The subjects fasted overnight for 12 h and continued to fast during the experimental procedure. A 1000 mg dose of each Ca salt was ingested at weekly intervals. Blood was drawn after 30, 60, 90, 120, 180, 240, 300 and 360 min for measurement of serum Ca, phosphorus (P), parathyroid hormone (PTH) and whole plasma calcitonin (iCT). All Ca supplements induced significant (+6.4% to +8.1%; p < 0.01) increases in Ca and significant suppression of PTH (-37.4% to -57.4%; p < 0.01). Comparison of response curves revealed significantly (p < 0.01) more marked Ca increase and PTH suppression with CC than with the other three Ca salts. CG' and CC induced marginal decreases in serum P and the overall curve of P variations was different for TCP compared with CG, CG' and CC. No significant variation of iCT was recorded during the test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Paget's disease of bone treated with a five day course of oral tiludronate.

Chloro-4-phenyl thiomethylene bisphosphonate (tiludronate) is a new drug which can be used as an inhibitor of bone resorption. As it remains in bone for a long time, and as mineralisation defects have only been seen at doses much higher than those required to decrease osteoclastic activity, it could be given at high doses over a short period of time. Eighteen patients with Paget's disease of bone were randomly allocated to three therapeutic groups receiving respectively 600, 800, and 1200 mg/day tiludronate for five days. Serum alkaline phosphatase activity and the urinary hydroxyproline/creatinine ratio were quickly and drastically reduced in all three groups. A significant reduction of serum alkaline phosphatases and the hydroxyproline/creatinine ratio was still present six months after the five day therapeutic course, reflecting a sustained activity of tiludronate even after stopping treatment. Dose dependent short and long term reductions of bone turnover rate were observed. Biochemical assessment of haematological, renal, or hepatic tolerance did not show any toxicity of tiludronate. Fifty per cent of patients treated by a dose of 1200 mg/day reported gastrointestinal disturbances, however, making this dosage unsuitable for clinical practice.

Administration, Oral↗

Minimal levels of serum estradiol prevent postmenopausal bone loss.

Biochemical parameters reflecting bone resorption [urinary calcium/creatinine (Ca/Cr) and hydroxyproline/creatinine (OH/Cr)] were related to serum estrogens [estrone (E1) and estradiol (E2)] in 262 healthy women including 158 patients receiving estrogen replacement therapy (ERT) for at least 6 months, 49 eugonadal women, and 55 untreated postmenopausal women. A significant (P < 0.001) correlation exists between serum E2 and Ca/Cr: Ca/Cr (mg/dl) = -0.00044 E2 (pg/ml) + 0.129 (n = 262; r = -0.37), serum E2 and OH/Cr: (OH/Cr (mg/g) = -0.049 E2 (pg/ml) + 18.76 (n = 262; r = -0.36), serum E1 and Ca/Cr: Ca/Cr (mg/dl) = -0.0003 E1 (pg/ml) + 0.127 (n = 261; r = -0.28) but not between serum E1 and OH/Cr. Women with circulating levels of E2 between 60 and 90 pg/ml have a significant (P < 0.01) reduction of Ca/Cr and OH/Cr when compared with those with lower levels of E2. Higher values of E2 do not provide additional benefit. We conclude that in postmenopausal women receiving an estrogen replacement therapy (ERT), a significant reduction of bone resorption is achieved when circulating levels of estradiol reach a value (60 pg/ml) corresponding to the one measured, in eugonadal women, during the last days of the early follicular phase of the menstrual cycle. We suggest that oral or percutaneous ERT should induce a minimal value of 60 pg/ml to prevent postmenopausal bone loss.

Analysis of Variance↗

Calcitonin metabolism in senile (type II) osteoporosis.

The exact role of calcitonin (CT) in the pathogenesis of senile (Type II) osteoporosis remains unknown. Whole plasma calcitonin (iCT) and extracted monomeric calcitonin (eCT) basal levels, metabolic clearance rate (MCR) and production rate (PR) of iCT and eCT were measured in 41 postmenopausal women, including 14 hip fractures (OP II) and 27 healthy controls. No significant difference appeared for basal iCT levels between OP II (mean +/- SEM: 41.9 +/- 3.4 pg/ml) and controls (mean +/- SEM: 46.2 +/- 5 pg/ml). eCT basal levels were similar in OP II (mean +/- SEM: 5.42 +/- 0.5 pg/ml) and in controls (mean +/- SEM: 7.3 +/- 0.7 pg/ml). MCR were similar in the two groups. iCT PR were similar in OP II (mean +/- SEM: 17.2 +/- 1.5 micrograms/24 h) and controls (mean +/- SEM: 18.6 +/- 1.1 micrograms/24 h). No difference appeared between eCT PR in OP II (mean +/- SEM: 2.3 +/- 0.2 micrograms/24 h) and controls (mean +/- SEM: 3.2 +/- 0.3 pg/ml). From these data, no evidence appears that calcitonin might be one of the determinant factors in the pathogenesis of senile osteoporosis.

Aged↗

Influence of estrogen replacement therapy on endogenous calcitonin production rates.

Calcitonin is now a well-accepted therapy for inhibition of bone loss, both in the first years of menopause and in established osteoporosis. However, its exact role in the pathogenesis of that disease as well as the interactions between calcitonin production and estrogen metabolism remain unsolved. In order to clarify the influence of estrogen replacement therapy (ERT) on calcitonin secretory capacity, we measured whole plasma immunoreactive calcitonin basal levels, metabolic clearance rates and production rates in a group of postmenopausal women, before and after a daily intake for 28 days of 0.625 mg/day of conjugated equine estrogens, and again 4 weeks after the withdrawal of that estrogen replacement therapy. No significant changes appeared in immunoreactive calcitonin or immunoreactive calcitonin metabolic clearance rate but the production rate significantly increased over the 28 days (mean +/- SEM, from 21.3 +/- 5.1 pg/ml to 25.2 +/- 5.9 pg/ml, p less than 0.05), and then decreased 4 weeks after therapy was withdrawn to the initial level (17.9 +/- 3.6 pg/ml). We concluded that estrogen replacement therapy significantly increases calcitonin secretory capacity. This confirms the interactions between calcitonin production and estrogen metabolism, and may provide an explanation concerning the mode of action of estrogen replacement therapy in prevention of postmenopausal bone loss.

Aged↗

Dual photon absorptiometry of lumbar spine in west European (Belgian) postmenopausal females: normal range and fracture threshold.

Bone mineral content (BMC) and bone mineral density (BMD) of lumbar spine have been measured in 695 healthy postmenopausal and 64 type I osteoporotic Belgian, Caucasian females. Bone loss is strongly correlated to time elapse from menopause (Tm) with a maximum rate of bone loss during the first five years of menopause. BMC (gHA) = 461 + 0.662 ln Tm -0.481 (ln Tm)2 and BMD (gHA/cm2) = 0.91 + 0.00711 ln Tm - 0.00846 (ln Tm)2 (in both cases p less than 0.001 and Tm expressed in months of menopause). After 20 years of menopause, 50 to 60% of normal women have vertebral BMC and BMD values below the 90th percentile of women with vertebral fractures and, thus, might be considered to have asymptomatic osteoporosis. We conclude that prevention of postmenopausal osteoporosis should be initiated as soon as possible after the onset of menopause and that bone density screening should be extended in elderly in order to detect and allow treatment of asymptomatic "densitometric" osteoporosis.

Absorptiometry, Photon↗

Calcitonin and postmenopausal bone loss.

In order to establish the role of calcitonin (CT) in postmenopausal bone loss, we studied CT metabolism in 25 pre- and postmenopausal women. Postmenopausal women presented a highly significant reduction of CT basal levels compared to premenopausal females (p less than 0.01). Also, production rates of CT in osteoporotics were significantly lower than in either young premenopausal (18-25 years old), older premenopausal (35-40 years old), or postmenopausal healthy subjects. In a study in rabbits, we found that injection of CT, along with equimolar amounts of anti-SCT antibodies extracted from serum of pagetic patients, did not inhibit the hypocalcemic response to the hormone, thus demonstrating that resistance to CT treatment cannot be accounted for by antibody production. In a subsequent clinical study in patients with Paget's disease of bone, we found that 200 IU/day of salmon CT (SCT), given by nasal spray, improved both clinically and biochemically the activity of the disease, as demonstrated by 37 +/- 4% decrease of serum alkaline phosphatase and 35 +/- 5% fall of urinary excretion of hydroxyproline after six months of therapy. The effectiveness of CT as nasal spray was further tested in healthy women at an early stage of menopause. A 12-month course of intranasal SCT counteracted early postmenopausal bone loss, presumably by inhibiting bone resorption. In conclusion, intranasal CT seems to be a very attractive alternative to be considered for the prevention of postmenopausal osteoporosis.

Administration, Intranasal↗

Relationship between whole plasma calcitonin levels, calcitonin secretory capacity, and plasma levels of estrone in healthy women and postmenopausal osteoporotics.

The exact role of calcitonin (CT) in the pathogenesis of postmenopausal osteoporosis remains unknown. Whole plasma calcitonin (iCT) basal levels, metabolic clearance rate (MCR), and production rate (PR) of CT were measured in 9 premenopausal and 16 postmenopausal women, including 11 osteoporotics (OP). Basal iCT levels were statistically lower in postmenopausal women than in the premenopausal group (P less than 0.01) and strongly correlated (r = 0.72; P less than 0.001) with estrone circulating levels (E1). MCR were similar in all groups. PR were similar in eugonadal women between 22 (mean +/- SD = 30.9 +/- 9.9 micrograms/d) and 37 yr (mean +/- SD = 25.5 +/- 11.1 micrograms/d) premenopausal women. In healthy postmenopausal women PR were reduced, but not significantly (mean +/- SD = 19.5 +/- 6.95 micrograms/d), whereas osteoporotic patients presented a highly significant reduction of CT PR (mean +/- SD = 9.8 +/- 4 micrograms/d) (P less than 0.01). Because there is a strong relationship between E1 and PR (r = 0.64; P less than 0.001), CT secretory capacity appears to be modulated by estrogen circulating levels. This modulation leads to a menopause-related decrease in iCT. In osteoporotics, an independent impairment of CT production drastically lowers PR and basal iCT levels. CT might be one of the determining factors in the pathogenesis of postmenopausal osteoporosis.

Adult↗

Preliminary report of decreased serum magnesium in postmenopausal osteoporosis.

Serum, red cell, urinary and bone Mg levels have been measured in 10 post-menopausal osteoporotics. Osteoporosis was confirmed by clinical fracture, histological analysis and dual-photon absorptiometry quantification. When compared to a healthy population matched for age and sex, serum Mg levels were statistically significantly (p less than 0.05) lower in osteoporotics (0.82 +/- 0.06 mmol/l) compared to normal subjects (0.87 +/- 0.04 mmol/l). No difference appeared for red cell, urinary or bone Mg determination. If these results are confirmed in a long-term study, serum Mg might be added to a batch of tests used to discriminate a subset of patients with an increased risk of developing postmenopausal osteoporosis.

Aged↗