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Biomedical subjects

D Agnusdei

Publications and source records attributed to D Agnusdei.

16 recordsLinked to original sources

An effective regimen of intranasal salmon calcitonin in early postmenopausal bone loss.

In order to devise a convenient and effective therapeutic regimen of intranasal salmon calcitonin (sCT) for the treatment of early postmenopausal bone loss, we studied the effects of a 1-year course of sCT nasal spray on vertebral mineral content (VMC), assessed by dual photon densitometry, and bone turnover in 21 early postmenopausal osteoporotic women. Subjects enrolled in the study had a value above the normal average of at least one index of bone turnover: whole body retention (WBR) of 99mTc-methylene-dichloro-bisphosphonate (99mTc-MDP), serum bone gla protein (BGP), urinary hydroxyproline/creatinine excretion (HOP/Cr). After baseline evaluation, patients were randomized for treatment with either sCT (200 IU every other day) or placebo. Treatment with sCT significantly increased VMC by 2.7 +/- 0.9% at 6 months, and 3.3 +/- 0.8% at 1 year, whereas a progressive decline was observed in the placebo group (-2.6 +/- 0.5%, and -3.5 +/- 0.5% after 6 and 12 months, respectively). These changes were associated with a progressive and significant reduction of all parameters of bone turnover in the sCT-treated patients, whereas no changes were detected in the control group during the study period. The differences between the two groups were significant after 1 year for VMC, BGP, and WBR (P less than 0.05, one-way analysis of variance). Thus, 200 IU intranasal sCT administered on alternate days is adequate to stop the fast bone loss occurring early after the menopause in women with high bone turnover rates. This therapeutical modality represents an important addition to the available pharmacologic spectrum for the prevention and treatment of postmenopausal osteoporosis.

Administration, Intranasal

Short-term treatment of Paget's disease of bone with ipriflavone.

Ipriflavone (IP), an isoflavone derivative, seems to prevent the loss of bone mass through the inhibition of bone resorption, mainly inhibiting the recruitment of osteoclasts. We investigated whether a brief course of treatment with IP can reduce biochemical parameters of accelerated bone turnover and bone pain in patients with active Paget's disease of bone. Sixteen patients (9 males and 7 females) with active Paget's disease were randomly allocated to two different crossed-over dose regimens of treatment with IP (600 mg/day vs. 1200 mg/day). Each treatment course lasted 30 days and the wash-out period between the two sequences was 15 days. Serum alkaline phosphatase (Al.Ph.) and urinary hydroxyproline/creatinine excretion (HOP/Cr) were reduced after each sequence. At the end of the 600/1200 mg/day treatment sequence, serum Al.Ph. and HOP/Cr decreased with 32% and 25.6% respectively. At the end of the 1200/600 mg/day treatment sequence, serum Al.Ph. and HOP/Cr decreased with 33% (P < 0.01) and 24.1% (P < 0.05) respectively. Furthermore, a significant decrease in bone pain was observed during the 1200/600 mg/day sequence (P < 0.01). Both treatment schedules were well tolerated and the patients' compliance resulted excellent. Our results indicate that short-term treatment with IP can reduce biochemical parameters of disease activity and bone pain in patients with active Paget's disease of bone.

Administration, Oral

Effects of ipriflavone on bone mass and calcium metabolism in postmenopausal osteoporosis.

Recently it has been demonstrated that ipriflavone (IP), an isoflavone derivative, is able to increase bone mass in patients with established postmenopausal osteoporosis (PMO). Here we present a preliminary report of a 2-year multicenter, double-blind, placebo-controlled clinical study performed in order to evaluate the efficacy and tolerability of IP in PMO. A large number of patients with PMO, referred to 12 Italian centers, was randomly divided into 2 groups and treated with oral IP (600 mg/day) or placebo (Pl). All patients received an oral Ca supplement (1 g/day). One hundred and twenty six patients completed 1 year of the study. Bone mineral density (BMD) of the distal radius, measured by DPA, serum osteocalcin (BGP), and urinary hydroxyproline excretion (HOP/Cr), were measured before and after 12 months. After 12 months, a significant increase in BMD was observed in the IP-treated group (P < 0.05). IP determined a reduction of HOP/Cr, while in Pl-treated patients a significant increase of this index, as well as of BGP, was observed. After 12 months the difference between the two groups resulted significant (P < 0.05) for BGP. The drug was well tolerated and the patients' compliance to the oral treatment resulted excellent. The results of this study indicate that IP is able to increase bone mass in patients with PMO.

Aged

Use of calcitonin in the treatment of bone pain associated with osteoporosis.

In osteoporosis, calcitonin exerts an analgesic effect that is unrelated to its effect on bone. Although the precise mechanism has yet to be clarified, there is some evidence that the analgesic effect of calcitonin may be mediated through the endogenous opioid system. The intranasal administration of calcitonin seems to be more effective in producing analgesia than parenteral administration.

Bone and Bones

Dose-response bioactivity and bioavailability of salmon calcitonin in premenopausal and postmenopausal women.

We investigated the acute, dose-response to three intranasal doses of salmon calcitonin (sCT) (50 IU, 100 IU, and 200 IU) and one im dose (50 IU) in eight premenopausal and eight early postmenopausal women. Total serum calcium and serum beta-endorphin revealed significant changes after all four administrations (P less than 0.05). After the two highest intranasal and the im doses cAMP increased 10% and 35%, respectively (P less than 0.05). All administrations except the 50 IU intranasal dose produced significant increases in plasma sCT (P less than 0.05). The areas under the concentration-time curves, calculated for the period with the maximal changes (i.e. 120-240 min), illustrated a significant dose-related response in total serum calcium, beta-endorphin, and sCT (P less than 0.01-0.001). cAMP showed a dose-related tendency, the response to the im injection being significantly higher than that to the two lowest doses of intranasal sCT (P less than 0.05). We conclude that the doses administered produce a dose-related biological response and bioavailability. In women with normal and high bone turnover, sCT 100 IU intranasally seems as optimal as 50 IU im. The response to sCT should, furthermore, be assessed on bioactivity rather than on bioavailability.

Administration, Intranasal

The effects of intravenous isoxsuprine on blood viscosity in patients with occlusive peripheral arterial disease.

1 Blood viscosity is thought to be a major factor in disorders of the peripheral circulation. 2 Ten patients with obliterative arterial disease received an infusion of isoxsuprine of 20 micrograms kg-1 for 30 min. The infusion was followed by a highly significant and prolonged fall in blood, plasma and serum viscosity, in haematocrit and in plasma fibrinogen concentration. Blood lipid levels were also studied: total lipids and total cholesterol did not alter; triglyceride level was significantly lowered at the end of, and after, drug infusion. 3 There was no change in blood, plasma or serum viscosity in the four patients receiving a control infusion 2 days before the infusion of isoxsuprine. 4 The relationships between lowered viscosity and increasing peripheral tissue perfusion are discussed.

Aged

[Action of dopamine on blood flow of the limbs and on blood viscosity (author's transl)].

The observation of several cases of gangrene in the lower limbs of subjects treated with an infusion of dopamine has encouraged the authors to study the action of the drug, in a dose capable of increasing the arterial pressure, on the blood flow in the lower limbs and on the viscosity of the blood in a group of normal middle aged subjects. A significant reduction in the values of the blood flow with a simultaneous increase in the blood viscosity was observed. There results confirm the ischemic action of the drug with the doses used at the muscular and cutaneous level in the lower limbs.

Blood Circulation

[Ultrasonography techniques in the evaluation of the osteoporotic patient].

Previous studies have shown a significant but weak correlation between speed of sound (SOS) and broadband ultrasound attenuation (BUA) in bone, and densitometric bone measurements. These findings indicate that these techniques reflect different properties of bone. We measured SOS and BUA in the os calcis (Achilles, Lunar Corp.) and bone mineral density of the lumbar spine (BMS-LS; by DEXA) and of the ultradistal radius (BMD-UDR; by DPA) in 60 postmenopausal women (age range 50-65): 30 were osteoporotic women (OP) and 30 were age-matched normal postmenopausal women (N). Mean values of SOS and BUA resulted significantly lower in OP group (p < 0.001). SOS and BUA measurements significantly correlated with DEXA of the lumbar spine (r = 0.52 p < 0.001, r = 0.56 p < 0.001, respectively) and DPA of ultradistal radius (r = 0.60 p < 0.001 and r = 0.62 p < 0.001, respectively). In conclusion, these techniques show good correlations with absorptiometric techniques. The best correlation has been found between BUA and DPA of ultradistal radius. Furthermore, US techniques are able to separate a normal from an osteoporotic population. Therefore, US techniques seem to be a useful tool for screening of osteoporotic disease.

Absorptiometry, Photon

Dietary L-lysine and calcium metabolism in humans.

Calcium deficiency contributes to age-related bone loss; consequently, any preventive approach to osteoporosis should include dietary Ca adjustment or supplementation. The ideal Ca supplement would yield the greatest bioavailability. Studies in animals have shown that dietary supplements with certain amino acids, particularly L-lysine, can increase Ca absorption. Therefore, we examined the potential effect of this essential amino acid on Ca metabolism in humans. In one study, the acute effects of an oral Ca load (3 g as CaCl2) administered with or without 400 mg of L-lysine were compared in 15 healthy and 15 osteoporotic women. In all cases, the oral Ca load determined a progressive increase in serum total Ca and Ca2+ and a concomitant decrease in neophrogenous cAMP. As expected, a progressive increase in urinary Ca excretion was also observed, except in the L-lysine-treated healthy subjects, who exhibited a blunted calciuric response to the Ca load. In a second study, the effects of a short-term dietary supplementation with either L-lysine, L-valine, or L-tryptophan (800 mg/day) on 47Ca fraction absorption were compared in 45 osteoporotic patients. L-Lysine but not L-valine or L-tryptophan significantly increased the intestinal absorption of the mineral. Our results suggest that L-lysine can both enhance intestinal Ca absorption and improve the renal conservation of the absorbed Ca. The combined effects may contribute to a positive Ca balance, thus suggesting a potential usefulness of L-lysine supplements for both preventive and therapeutic interventions in osteoporosis.

Adult

[Ultrasound transmission velocity in the patella of normal subjects and in patients with postmenopausal osteoporosis].

Recently, ultrasound transmission velocity (UTV) has been used to assess skeletal status. The basic principle of UTV measurement of bone is that the speed at which ultrasounds propagate in bone is determined by the mass density and by the index of elasticity, which is intimately correlated with bone strength. Theoretically UTV should provide more information about bone fragility than the absorptiometric techniques of measurement of bone mass. To test this hypothesis, UTV was measured using the SIGNET(TM) (Osteo Technology, Framingham, MA, USA) in the patella of 79 postmenopausal nonobese women. The subjects were divided into 2 groups: 29 postmenopausal normal women (NPM) and 50 patients with at least one vertebral crush fracture due to postmenopausal osteoporosis (PMO). Besides UTV measurements in all subjects lumbar spine bone mineral density (BMD) was measured by dual energy Rx (Hologic QDR 1000). UTV in NPM (mean age 57.9 +/- 8 SD years) averaged 1867 +/- 62 m/sec, and in PMO (mean age 63.5 +/- 7.8 SD years) averaged 1771 +/- 74 m/sec. It follows that the difference between the two groups was about 96 m/sec. UTV correlated significantly with BMD measured in the lumbar spine (r = 0.51; p less than 0.001), giving a discrimination power virtually identical to that obtained by using spine BMD values. This preliminary data are promising for the use of this new technique which offers a simple, noninvasive measure of bone quality without the limitation of radiation exposure.

Aged