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Biomedical subjects

P Geusens

Publications and source records attributed to P Geusens.

At least 19 recordsLinked to original sources
PubMed1992

Evaluation of the efficacy and safety of oral tiludronate in Paget's disease of bone. A double-blind, multiple-dosage, placebo-controlled study.

OBJECTIVE: To assess the optimal dosage of oral tiludronate in Paget's disease of bone. METHODS: We studied 149 patients with Paget's disease, in a double-blind, randomized, placebo-controlled trial. Patients were randomly assigned to 1 of 5 therapeutic groups: a daily dose of 100 mg, 200 mg, 400 mg, or 800 mg of oral tiludronate, or a placebo. Treatment was for 3 months, followed by 3 months of placebo-controlled followup. Serum alkaline phosphatase activity (SAP) and fasting urinary excretion of hydroxyproline/creatinine (OH/Cr) were measured monthly, as were biochemical parameters reflecting renal, hepatic, and hematologic functions. Analgesic efficacy was self-evaluated from a visual analog scale and a global pain index. RESULTS: Statistical analysis revealed that beginning at a dosage of 200 mg/day, there was a direct dose-dependent effect on the reduction of SAP and OH/Cr levels. Reduction of SAP levels was clinically significant at a dosage of 400 mg (44.9 +/- 4.2% reduction at 90 days and 49.2 +/- 4.5% at 180 days, mean +/- SEM) and at 800 mg (53.4 +/- 5% at 90 days and 59.3 +/- 4.6% at 180 days). There was a significant reduction in pain in all groups, including the group taking placebo. In only those taking 800 mg/day of tiludronate was there a significant frequency of complete resolution of pain (versus placebo). Aside from mild gastrointestinal disturbances, as experienced with other oral bisphosphonates, clinical tolerance of all 5 regimens was good. Exhaustive biochemical investigations failed to reveal significant toxicity of tiludronate up to the 800-mg daily dose investigated. CONCLUSION: Because of its significantly better antiresorptive effects and greater analgesic properties (compared with lower dosages), combined with the excellent clinical and biochemical tolerance, the 800-mg daily dose of tiludronate appears to be optimal for the treatment of Paget's disease of bone.

Administration, Oral↗
PubMed1992

Longitudinal effect of tiludronate on bone mineral density, resonant frequency, and strength in monkeys.

The effect of Tiludronate on bone was studied in 72 growing monkeys (Papio papio), 36 males and 36 females, aged 4-7 years. They were randomly allocated into four groups (18 animals per group, 9 males and 9 females): group I, controls; group II, 10 mg/kg/day; group III, 20 mg/kg/day; and group IV, 40 mg/kg/day of Tiludronate. A total of 12 animals (6 males and 6 females) in each group were sacrificed at the end of treatment (1 year) and 6 animals (3 males and 3 females) per group 1 year later. Bone mineral density (BMD) was measured by dual-photon absorptiometry. Biomechanical properties were evaluated by an impact torsion test and by resonant frequency analysis. Bone mineral measurements indicated that at the end of 1 year of treatment BMD was significantly higher, especially at the distal epiphysis of the radius, than in controls. No significant differences between groups were found in BMD 1 year after stopping treatment. Biomechanical analyses indicated that torsional stiffness increased after treatment. No differences between groups were found 1 year after stopping treatment. Results of resonant frequencies indicated an increased calculated transversal stiffness after treatment and 1 year later and an increased buckling strength 1 year after stopping treatment. In conclusion, the results on the effect of Tiludronate in growing monkeys indicate a profound effect of this drug on bone density and biomechanical properties. The biomechanical results indicate that this drug is safe, with conservation of bone strength despite a change in intrinsic mechanical properties of the bone.

Animals↗
PubMed1992

Bone and mineral metabolism in the adult guinea pig: long-term effects of estrogen and androgen deficiency.

The effects of androgen and estrogen deficiency on skeletal homeostasis were studied in the guinea pig. Male and female adult (7 months old) guinea pigs were either sham operated (9 females and 7 males) or gonadectomized [9 ovariectomized (OVX) females and 6 orchidectomized (ORX) males] and sacrificed 4 months later for evaluation of bone mass, bone turnover, and serum calcium homeostasis. Parameters of bone turnover, calcium homeostasis, and vitamin D metabolites were similar in all groups except for increased serum IGF-I concentrations (+30%) in males compared to females. Gonadectomy resulted in a 50% decrease in serum IGF-I concentrations in males only (p < 0.001). Volume, total calcium content, and cortical density of the tibia were significant higher in males than in females. Estrogen deficiency had no effect on bone volume or calcium content. Androgen deficiency resulted in a significant lower volume and calcium content of the tibia and in a lower calcium content of the distal lumbar vertebrae. Single-photon absorptiometry of the tibia showed that only cortical, not trabecular bone density of the tibia was decreased after ORX. Histomorphometric studies of the tibial metaphysis also did not show significant differences in trabecular bone volume between sham-operated and ORX males. We conclude that in adult male guinea pigs androgen deficiency results in a decrease in (cortical) bone volume and content concomitant with decreased IGF-I levels. In female guinea pigs of the same age, estrogen deficiency did not affect total or regional bone mass.

Absorptiometry, Photon↗
PubMed1992

Chloroquine levels in blood during chronic treatment of patients with rheumatoid arthritis.

Blood levels of racemic chloroquine and its main metabolites desethylchloroquine and bisdesethylchloroquine were measured in 29 patients treated chronically for rheumatoid arthritis. In six patients, the concentrations were followed during a one day dosage interval. There was considerable intersubject variability in the steady state blood concentrations of chloroquine (range 36.6 to 3895 ng.ml-1) and its two main biotransformation products; the latter represented, respectively, 47.7% and 12.9% of the concentration of chloroquine. This finding shows the need for further studies in view of the known toxic effects of chloroquine and the inevitable accumulation due to the exceptionally long residence time of the compound and its metabolites. The main requirement, which has not yet been met, for adding chloroquine to the list of drugs for which therapeutic drug monitoring is useful, is the lack of information about its mechanism of action, and consequently the dose-effect relationships of its therapeutic and toxic actions. Regular ophthalmic examination, in particular, is strongly recommended. The relatively high concentrations of desethylchloroquine and bisdesethylchloroquine found during chronic treatment show the need for more information about the therapeutic value and adverse effects of the metabolites.

Adult↗
PubMed1992

Alterations of the mineralization profile and osteocalcin concentrations in osteoarthritic cortical iliac crest bone.

The relation between bone mineralization and osteocalcin content was investigated in iliac crest cortical bone obtained at necropsy in young females and in two groups of elderly women with and without osteoarthritis of the hands evaluated by X-ray. Using density fractionation technique, the bone was separated into fractions of increasing density from 1.72 to 2.30 g/ml. The mineralization profile revealed a significant shift to higher densities in the osteoarthritis cases compared with young adults (P less than 0.005) and age-sex-matched controls (P less than 0.001). The ash, calcium, and phosphorus content of the bone increased with increasing density of the fractions whereas collagen content, measured as hydroxyproline, decreased. The osteocalcin concentration of each fraction was determined in the supernatants obtained after EDTA-extraction in the presence of protease inhibitors. In the young control and osteoarthritis group, the osteocalcin content in the lowest density fractions was higher compared with the older non-osteoarthritic group. Osteocalcin content of the high density fractions, representing highly mineralized osteons, was the same in the three groups studied. These findings support the hypothesis that quality differences in bone may explain the inverse relationship between osteoarthritis and osteoporosis.

Adult↗
PubMed1992

Intranasal calcitonin for the prevention of bone erosion and bone loss in rheumatoid arthritis.

The effect of intranasal salmon calcitonin on pain, erosion progression, and bone loss in 40 women with rheumatoid arthritis was investigated. The study design was double blind, placebo controlled for the first four months and open for the next 36 months, allowing for cross over to active drug treatment or to the control group. Morning stiffness was reduced in the group treated with salmon calcitonin after two and four months. After an average follow up of 28 months no significant effect on erosion progression was observed using the Larsen score. The mean (SD) monthly progressions in the Larsen score in the calcitonin and control groups were 0.21 (0.22) and 0.23 (0.28) respectively. The bone mineral density was evaluated in the forearm and spine. During the 12 months of follow up the control group lost bone at a rate of 2%/year at the spine and 4.8%/year at the radius distal third. In contrast, the group receiving nasal calcitonin gained 1% in bone mineral density at the lumbar spine and no loss at the radius distal third. The increase in bone density at the spine in the calcitonin group was not sustained and a loss of 1.8%/year was observed in the second year. The difference with the placebo group remained significant.

Administration, Intranasal↗
PubMed1991

Calcium-deficient diet in ovariectomized dogs limits the effects of 17 beta-estradiol and nandrolone decanoate on bone.

Postmortem measurements by dual-photon absorptiometry of the femur and the second lumbar vertebra in adult dogs indicated bone loss after ovariectomy, which was more pronounced when calcium-deficient diet was given in ovariectomized dogs. This bone loss was nonhomogeneous throughout the femur. Ovariectomy resulted in trabecular and cortical bone loss, and additional calcium-deficient diet resulted in a further highly significant trabecular bone loss at the proximal epiphysis of the femur and in the vertebra. This bone loss was presumably the result of increased bone turnover, as reflected by the highly significant increase in serum alkaline phosphatase. Estrogens could only partially prevent the bone loss induced by calcium deficiency after ovariectomy, and nandrolone decanoate was not effective. We conclude that (1) ovariectomy results in bone loss in adult dogs, (2) this bone loss is more pronounced after calcium-deficient diet, (3) calcium deficiency could be a limiting factor for the preventive effect of estrogens and nandrolone decanoate, and (4) dual-photon absorptiometry allows the evaluation of nonhomogeneous bone loss throughout excised bones.

Absorptiometry, Photon↗
PubMed1991

Relative risk factors for osteoporotic fracture: a pilot study of the MEDOS questionnaire.

This study tested selected elements of a questionnaire devised to detect risk factors for osteoporosis in a large case-control study of hip fracture. The questions were applied to two separate studies. The first utilised a hospital sample of postmenopausal women with established vertebral osteoporosis, and responses were compared to woman with primary osteoarthritis. In a second study, the questionnaire was applied to apparently healthy women participating in a study of bone density. Significant differences between patients with osteoporosis and osteoarthritis were observed in body mass index, the prevalence of appendicular fractures, the degree of immobilisation, the age of menarche, exposure to sunlight and indices of physical activity. Significant differences were found in bone mass in healthy women divided according to the age of menarche, parity and duration of lactation. These data identify previously established risk factors for osteoporosis and suggest that the MEDOS questionnaire will provide a powerful tool for the future assessment of risk factors in osteoporosis.

Adult↗
PubMed1991

Prevention and treatment of osteopenia in the ovariectomized rat: effect of combined therapy with estrogens, 1-alpha vitamin D, and prednisolone.

The effects of estrogens and 1-alpha were studied in young animals after ovariectomy (OVX) and/or prednisolone (PDN). These medications were given separately or in combination as preventive therapy from the start of the experiment, and as curative therapy starting 3 months later. Changes in bone mass were evaluated by single photon absorptiometry of the femur at the diaphysis (containing mostly cortical bone) and at the distal end of the femur (containing mostly trabecular bone). Radiogrammetry was performed at 50% of the length of the femur. Estrogens prevented further bone loss after OVX and OVX + PDN, given either at the beginning of the experiment or started 3 months later, except for trabecular bone loss immediately after OVX + PDN. After 1-alpha vitamin D, a highly significant increase in BMC and BMD was found in controls, in animals treated with PDN, and after OVX and OVX + PDN. The combination of 1-alpha with estrogens was less effective than 1-alpha but more effective than estrogens alone. After correction for body weight changes globally the same results were found. We conclude that (1) estrogens prevent bone changes after ovariectomy and ovariectomy + prednisolone; and (2) 1-alpha vitamin D highly significantly increased bone mass in male and female rats, and after prednisolone treatment, ovariectomy, and ovariectomy + prednisolone treatment.

Animals↗
PubMed1991

Short-term course of 1,25(OH)2D3 stimulates osteoblasts but not osteoclasts in osteoporosis and osteoarthritis.

We investigated the effect of short-term, 1,25-dihydroxyvitamin D3 therapy (4 micrograms/day for 4 days) on calcium metabolism in 27 postmenopausal women (11 cases with osteoporosis and 16 cases with osteoarthritis). Bone mass at the axial and appendicular skeleton was higher in osteoarthritis than in osteoporosis. Initial values of calcium metabolism were similar. Osteoporotic and osteoarthritic patients responded with a similar significant increase in serum osteocalcin (+61% and +54%, respectively), fasting urinary calcium excretion (+178% and +124%, respectively) and 24 hour calcium excretion (+148% and +142%, respectively). Parathyroid hormone (PTH) levels decreased significantly in both groups (-30% and -18%, respectively). Osteoclastic bone resorption, evaluated by urinary hydroxyproline excretion, was not stimulated in either group. We conclude that in osteoporosis and also in osteoarthritis (1) 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) stimulation of osteoblast function is similar in production of osteocalcin; (2) the vitamin D target tissues react adequately to 1,25(OH)2D3 stimulation; (3) short-term high dose of 1,25(OH)2D3 does not stimulate bone resorption; and (4) the differences in bone mass between osteoarthritis and osteoporosis are not related to an alteration of the responsiveness to stimulation by 1,25 (OH)2D3.

Aged↗
PubMed1991

Seasonal variation in bone metabolism in young healthy subjects.

Serum vitamin D metabolites and urinary calcium excretion; parameters of bone formation (serum alkaline phosphatase, serum osteocalcin); parameters of bone resorption (24 hour hydroxyprolinuria, 2 hour fasting urinary hydroxyproline/creatinine ratio); and parameters of cortical and trabecular bone density, parathyroid hormone (iPTH, COOH terminal assay), and serum minerals (calcium, phosphorus) were followed serially in 55 young adults (21 women and 34 men) from December 1985 until January 1987 at four different times during the year. The effect of a low-dose cyclooxygenase inhibitor (piroxicam 5 mg daily) on the same parameters of bone density and bone turnover when given from December until May, was also evaluated in this study. At the end of the treatment period parameters of bone turnover and bone density were comparable between placebo and piroxicam-treated groups. Therefore, the results of all subjects were pooled in order to investigate seasonal variation. In both sexes, seasonal variation was found not only for 250HD3 but also for 1,25(OH)2D3, serum calcium and phosphorus, urinary calcium excretion, and for bone density at the lumbar spine. Parameters of bone formation (serum osteocalcin and alkaline phosphatase), bone resorption (24 hour urinary hydroxyprolinuria and fasting urinary hydroxyproline/creatinine ratio) and PTH were influenced by this seasonal variation. We conclude that in young adults, a significant seasonal variation occurs, with low winter and high summer values, for serum 25 and 1,25(OH)2D3 for urinary calcium apparently without important influence on parameters of bone turnover or parathyroid activity and for lumbar spine density. Treatment with a low-dose cyclooxygenase inhibitor was without influence on the observed changes.

Adult↗
PubMed1991

Non-linear increase in vertebral density induced by a synthetic steroid (Org OD 14) in women with established osteoporosis.

The results of a 2-year placebo-controlled study in 38 female patients with osteoporosis are presented. This study was conducted to evaluate the efficacy of a daily oral dose of 2.5 mg Org OD 14 ((7 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one) in the treatment of established osteoporosis. Org OD 14 is a steroid which shows combined weak oestrogenic, androgenic and progestational activity. A total of 31 patients completed a 12-month study period (17 placebo, 14 Org OD 14) and 25 of these went on to complete the full 24-months (15 placebo, 10 Org OD 14). A significant increase in bone mineral density as measured by dual photon absorptiometry was recorded in the lumbar spine in the Org OD 14-treated patients at 8, 16 and 24 months. The gain in bone mass after 8 months averaged 4% (P less than 0.01) and after 24 months 8% (P less than 0.001). In the control group, a bone loss rate of 2% per year was recorded in the lumbar spine. No significant changes in bone density in the forearm as assessed by single photon absorptiometry were found in either group. The increase in spinal bone density in the Org OD 14 group was non-linear and followed an S-shaped upward pattern. Org OD 14, while inducing no appreciable endometrial stimulation, was found to be a bone-active compound with anti-resorbing as well as anabolic activity. Org OD 14 warrants consideration not only for the long-term prevention of bone loss but also for curative treatment of post-menopausal osteoporosis.

Absorptiometry, Photon↗
PubMed1991

Heterogeneity of growth of bone in children at the spine, radius and total skeleton.

Bone mineral content (BMC), density (BMD), and size were measured in 202 subjects ranging from 3 to 25 years of age (106 males and 96 females), half of which were children and half young adults. BMC and BMD were measured using single photon absorptiometry at the proximal and distal radius and dual photon absorptiometry at the lumbar spine and the total body. In the pre-pubertal age group (3-9 yrs), no differences were found in BMC nor BMD between males and females at any site. Growth of bone during puberty was characterized by an increase in BMC, bone size and BMD. The percent increase in BMC was greater at the lumbar spine and the total body (+200 to +390 %) than at the radius (+90 to +270 %). The increase in BMC was higher than the increase in BMD (+50 to +90 %). Overall bone growth in the total body was not reflected by changes in BMC of the appendicular skeleton. The increase in BMD was heterogeneous and was higher in the legs than in the arms. In males, the increase in BMC and size during growth was greater than in females resulting in a higher peak bone mass and size in males. The increase in BMD was similar between males and females at the distal radius, the lumbar spine and the total body, but higher at the proximal radius, the arms and the legs in males.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1991

1,25-Dihydroxyvitamin D3 stimulation test and the effect of a prostaglandin synthesis inhibitor (piroxicam) in young adults.

This study was performed to assess whether the 1,25(OH)2 vitamin D3 stimulation test for osteoblastic function is influenced by a prostaglandin synthesis inhibitor (piroxicam). Thirty-four healthy male young adults had a 1,25(OH)2 vitamin D3 (Rocaltrol) stimulation test. After a baseline day, the subjects received 2 micrograms Rocaltrol every 12 h for 4 days. Serum and urinary parameters of bone turnover were assessed before and after stimulation. The subjects were randomly allocated to placebo or piroxicam 5-, 10- and 20-mg treatment groups. After stimulation, serum and urinary calcium increased significantly, and immunoreactive PTH decreased significantly in the control group. In the piroxicam group, serum calcium, phosphate, osteocalcin and urinary calcium increased significantly, and PTH and glycosaminoglycan excretion significantly decreased. The piroxicam treatment group did not differ from controls, except for a nonsignificant minor increase in serum calcium and phosphorus after calcitriol stimulation. Since the major effect of nonsteroidal anti-inflammatory drugs is to decrease prostaglandin synthesis, these data suggest that prostaglandins do not mediate the effects of calcitriol on bone and other target tissues, because no alteration in intestinal calcium absorption, calcium-phosphorus-PTH interaction, bone turnover and renal handling of calcium and phosphorus in normal subjects was found.

Adult↗