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P Geusens

Publications and source records attributed to P Geusens.

At least 73 records · Page 4Linked to original sources
PubMed1995

Nandrolone decanoate: pharmacological properties and therapeutic use in osteoporosis.

The therapeutic profile on bone of nandrolone decanoate is that of inhibitor of bone resorption with temporary increase in bone formation, followed by an absence of suppression of bone formation, indicating uncoupling of bone resorption and formation. This results is an increase in bone mineral content at the proximal and distal radius, and in some patients at the lumbar spine. Furthermore, nandrolone decanoate increases calcium balance and muscle mass, diminishes vertebral pain and increases the mobility of the spine. Virilization occurred in around 50% of the patients (mainly hoarseness and/or hirsutism), and 9% of the patients dropped out because of this reason. A dose of 50 mg every 3 to 4 weeks is indicated in the treatment of osteoporosis in women, especially when they have low muscle mass, associated debilitating disease, and in patients with corticosteroid induced osteoporosis. It should only be prescribed after the age of 65 to 75 years to minimize the occurrence of clinical adverse effects and to increase its tolerability, which is higher in this group. Although some effects are reported on fracture rate, insufficient prospective data are available.

Aged↗
PubMed1995

Peptide transporter genes (TAP) polymorphisms and genetic susceptibility to rheumatoid arthritis.

The association of rheumatoid arthritis (RA) with HLA-DRB1 alleles indicates that at least one RA susceptibility gene is linked to the HLA class II region. Transporter associated with protein processing (TAP) genes, which lie upstream of the HLA-structural genes, may also contribute to disease susceptibility. We investigated polymorphisms of the peptide transporter genes, TAP 1 and TAP 2, by PCR-ASO hybridization techniques in 82 RA patients and 66 control individuals. Although there was a suggestion of linkage between some TAP polymorphisms and RA, these seem to be dependent on HLA-DRB1*04, since these positive associations disappeared when HLA-DRB1*04 positive RA patients and controls were compared. Furthermore, no particular TAP allele or haplotype was associated with any clinical or immunological subgroup of RA. We conclude that the TAP genes do not have a major influence on susceptibility to RA in the European Caucasian population.

Adult↗
PubMed1994

Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. A 12-month, double-blind, controlled study.

OBJECTIVE: To study the long-term effects of supplementation with omega-3 fatty acids (omega 3) in patients with active rheumatoid arthritis. METHODS: Ninety patients were enrolled in a 12-month, double-blind, randomized study comparing daily supplementations with either 2.6 gm of omega 3, or 1.3 gm of omega 3 + 3 gm of olive oil, or 6 gm of olive oil. RESULTS: Significant improvement in the patient's global evaluation and in the physician's assessment of pain was observed only in those taking 2.6 gm/day of omega 3. The proportions of patients who improved and of those who were able to reduce their concomitant antirheumatic medications were significantly greater with 2.6 gm/day of omega 3. CONCLUSION: Daily supplementation with 2.6 gm of omega 3 results in significant clinical benefit and may reduce the need for concomitant antirheumatic medication.

Anti-Inflammatory Agents↗
PubMed1994

Brittle bones in spontaneously diabetic female rats cannot be predicted by bone mineral measurements: studies in diabetic and ovariectomized rats.

Spontaneously diabetic BB rats were sham operated (SO) or ovariectomized (OVX) within days after onset and studied after 4, 8, and 12 weeks. Analyses included histomorphometry of proximal tibial metaphyses, biochemical analyses of humeri, DXA analyses, and biomechanical testing of femora. In SO diabetic rats, no osteoblasts, osteoid tissue, or osteoclasts were present on the trabecular bone surface, but trabecular bone volume (TBV) remained normal compared with control BB rats. The concentration of IGF-I per dry weight of humerus was decreased after 12 weeks of diabetes, whereas the concentrations of calcium and osteocalcin did not change. DXA analysis showed normal bone mineral density (BMD) at both diaphyseal and metaphyseal femoral areas. On biomechanical testing, angular deformation, energy absorption, and torsional strength of the femora were decreased after 8-12 weeks of diabetes, but stiffness was normal. Ovariectomy in diabetic rats caused a decrease in femoral BMD especially at the metaphysis, and there was a trend toward decreased TBV in the tibial metaphysis; TBV loss was less marked than in control OVX rats, however. The increase in BMD at the femoral diaphysis, measured after 12 weeks of OVX in control rats, was absent in diabetic rats. Multiple-regression analysis indicated that the presence of diabetes but not ovariectomy, weight, and mineral content correlated with decreased energy absorption, angular deformation, and strength of the femora. The data infer that the (near) absence of unmineralized bone matrix in severely diabetic rats alters bone microarchitecture and ultimately results in brittle bones, which is not predicted by BMC or BMD measurements.

Absorptiometry, Photon↗
PubMed1994

Effect of 1 alpha-vitamin D3 on bone strength and composition in growing rats with and without corticosteroid treatment.

The effects of 1 alpha-vitamin D3 were studied for 6 months in 2-month-old male and female rats on a moderately low calcium diet with or without low-dose prednisolone treatment. Both cortical bone mechanical and biochemical properties were examined. Femoral bone specimens were subjected to torsional loading tests. With age, bone strength and stiffness increased in both sexes, accompanied by an increased degree of mineralization (bone ash and calcium concentrations). During growth, strength and stiffness increased more in male than in female rats. When 1 alpha-vitamin D3 (0.5 micrograms/kg/day) was given alone, bone mechanical competence improved significantly whereas insulin-like growth factor-I (IGF-I) and calcium concentrations in the bone matrix were significantly reduced. Treatment with low-dose prednisolone (0.5 mg/kg/day) alone did not influence bone mechanical properties compared with intact control rats (without prednisolone) although a significant reduction in calcium concentration and an increased phosphorus concentration were measured. A combined therapy with prednisolone and 1 alpha-vitamin D3 significantly increased bone strength, toughness, and stiffness compared with control bones. Both mineralization degree (ash and calcium concentration) and IGF-I concentration were decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Androgen resistance and deficiency have different effects on the growing skeleton of the rat.

Mature male, female, and androgen-resistant testicular feminized (Tfm) male rats of the same strain were sacrificed at the age of 120 days. Young male and Tfm rats were orchidectomized (orch) at 1 month of age and sacrificed at 120 days. The right femora were dissected, cleaned, defatted, and scanned with the Hologic QDR-1000. Orch and Tfm rats had similar body weights that were intermediate between body weights of their normal male and female littermates. Serum IGF-I concentrations were lowest in Tfm rats; IGF-1 concentrations in orch rats were not lower than in males. Dual-energy X-ray absorptiometry yielded the following results: Total femoral mass and area were lower in female, Tfm rats and in both orch groups compared with intact male rats. Femoral bone density was, however, only decreased in orch rats. Bone density measured in an area containing only cortical bone was not different between groups. However, the density was lower in orch rats in an area containing both cancellous and cortical bone. This finding is consistent with a +/- 50% decrease of cancellous bone volume in orch rats compared with all other groups at the proximal tibial metaphysis (an area containing mainly cancellous bone). These data show that Tfm rats, despite having lower IGF-I levels in serum, low body weight, and decreased femoral areas, manage--in contrast with orchidectomized rats--to maintain similar trabecular bone densities and volumes during growth. We conclude that trabecular bone densities can be preserved in androgen-resistant male rats independent of bone or body growth velocity or IGF-I secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1994

Total body mineral mass measured with dual photon absorptiometry in healthy children.

Using dual photon absorptiometry, bone mineral content (BMC) and bone mineral density (BMD) of the total body and the lumbar spine were assessed in 97 healthy, Caucasian children aged 3-14 years. Excellent correlations were found between BMC and BMD on the one hand and age, body height and body weight on the other. No differences were found between boys and girls. There was a strong correlation between lumbar spine measurement as compared to those of the total body. Regression equations for total body and the different parts of the skeleton were calculated with either BMC or BMD as the dependent variable, and age, body height and body weight as independent variables. High variation coefficients were obtained in these multiple regressions, except for the head. For total body BMC and total body BMD, growth charts were constructed using Tanner and Whitehouse data on body height and body height and body weight. Conclusions. The increase in total body mineral content is an important feature of normal growth. Normal data for BMC and BMD in childhood are essential for bone mineralisation abnormalities in paediatric patients.

Absorptiometry, Photon↗
PubMed1994

T cell receptor delta locus polymorphism in rheumatoid arthritis.

In order to identify new susceptibility markers for Rheumatoid Arthritis (RA), we analysed the dinucleotide repeat polymorphism at the T cell receptor delta locus (TCRD) in 65 RA patients and 99 healthy Belgian controls. A significant under-representation of the A4-A5 TCRD genotype was observed in the RA population.

Alleles↗
PubMed1994

HLA class II and T-cell receptor beta chain polymorphisms in Belgian patients with rheumatoid arthritis: no evidence for disease association with the TCRBC2, TCRBV8 and TCRBV11 polymorphisms.

OBJECTIVES: To investigate whether T-cell receptor (TCR) beta chain germline alleles, either alone or in combination with a particular HLA-genotype, are associated with rheumatoid arthritis (RA). METHODS: Three restriction fragment length polymorphisms (RFLPs), detected with TCR constant (TCRBC2) and variable (TCRBV8, TCRBV11) gene segments were analysed in a representative group of Belgian, HLA class II-typed patients with RA, and in a group of Belgian control subjects. RESULTS: The study confirmed the known association of RA with the HLA-DRB1*0401/0404 genotype (RR = 2.14, 95% CI = 1.16-4.00) in the Belgian RA population. This association was even more pronounced in the patients with more severe RA (RR = 3.26, 95% CI = 1.55-6.89). These data suggest that the HLA-DRB1*04 genotype can be used as a marker for disease severity. Similar frequencies in patients and controls were observed for all TCRB RFLPs studied, and this was in spite of subgrouping the RA population according to criteria for disease stratification. CONCLUSION: While a clear association with HLA DRB1*0401/0404 is observed, no interactive effects were seen with RA, DR4, TCRBC2 and TCRBV alleles, implying that the combined presence of these polymorphic markers does not cause an increased susceptibility to RA, and does not predispose for more aggressive RA, nor for familial aggregation of the disease. These results argue against the hypothesis that TCRB polymorphisms play a crucial role in the susceptibility for RA.

Adult↗
PubMed1993

Mechanical properties, bone mineral content, and bone composition (collagen, osteocalcin, IGF-I) of the rat femur: influence of ovariectomy and nandrolone decanoate (anabolic steroid) treatment.

Nandrolone decanoate (ND) is an anabolic steroid with a positive effect on bone mass in osteoporotic patients. The mechanism of action, (i.e., reduction of bone resorption and/or stimulation of bone formation), the ultimate effect on mechanical properties, and the most effective dosage are not yet clear. To address these issues, dose-related effects of the long-term effect of ND on serum and bone biochemistry, bone mineral content, and bone mechanical properties in ovariectomized (OVX) rats (12 weeks old at the start of the experiment) were studied for 6 months. The results were compared with those obtained in age-matched, intact, and OVX rats. OVX caused in the femur a significant increase in net periosteal bone formation and net endosteal bone resorption of bone collagen content and torsional strength, and of serum alkaline phosphatase, osteocalcin, and insulin-like growth factor-I (IGF-I) levels, whereas cortical bone density and calcium/creatinine and phosphorus/creatinine in 24-hour urine were significantly reduced. Treatment of OVX rats with 1 mg ND/14 days resulted in a significant increase in periosteal bone formation, femur length, cortical and trabecular bone mineral content and density, torsion stiffness and strength, and bone IGF-I content, and a decrease in serum osteocalcin, urinary calcium/creatinine levels, and bone collagen content compared with OVX controls. The higher ND dosage of 2.5 mg/14 days did not improve the results. ND treatment did not reverse all changes induced by OVS to the level of the intact controls. These results indicate that ND acts as an antiresorptive drug and as a home formation stimulating drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Anabolic Agents↗
PubMed1993

The aged male rat as a model for human osteoporosis: evaluation by nondestructive measurements and biomechanical testing.

Effects of androgen deficiency and androgen replacement on bone density, as measured with dual-energy X-ray absorptiometry (DXA) and single photon absorptiometry (SPA), cortical ratio (cortical thickness/outside bone diameter x 100), and biomechanical properties were evaluated in 14-month-old (1 month after orchiectomy (orch) or sham-operation) and in 17-month-old (4 months after orch or sham) male rats. Whole femoral bone mineral content (BMC) and density (BMD) measured with DXA were not significantly decreased 1 month after orch. Whole femoral BMC and BMD were 10% and 8% lower in 4 months after orch (P < 0.01 and P < 0.001, respectively). This decrease was prevented by testosterone replacement. There was an excellent correlation (R = 0.99) between whole femoral BMC and femoral ash weight. Selective scanning of cortical and cancellous sites of the femur showed that both cancellous and cortical BMC and BMD were significantly decreased 4 months after orch. SPA of the right tibia confirmed a 7% decrease in cancellous BMC and BMD 4 months after orch (preventable by testosterone) but not in cortical BMD and BMC. Femoral cortical ratio decreased with age (47 +/- 2 in 14-month-old and 40 +/- 2 in 17-month-old sham rats versus 63 +/- 1 in 6-month-old male rats) due to a continuously enlarging femoral shaft. Androgen deficiency resulted in an even greater decrease of the cortical ratio 4 months after orch (36 +/- 2 in 17-month-old orch rats) that was again prevented by testosterone (47 +/- 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1993

The relation between resonant frequencies and torsional stiffness of long bones in vitro. Validation of a simple beam model.

The results of vibration analysis experiments and impact torsion tests performed on excised animal long bones were used to validate a simple beam model for the prediction of torsional stiffness from resonant frequencies. Resonant frequency data on two mutually perpendicular bending vibration modes of 142 excised long bones were evaluated. Torsional stiffness of the same bones had been determined by an impact torsion test. Using a simple beam model, a theoretical relation between resonant frequencies and torsional stiffness was derived. If total bone mass and bone length are known, the formula thus derived allows one to calculate torsional stiffness from resonant frequencies. Linear regression analysis shows a strong correlation between the measured and the calculated torsional stiffness for sheep femora (r2 = 0.63, n = 24), dog femora (r2 = 0.94, n = 34), dog tibiae (r2 = 0.79, n = 18) and monkey radii (r2 = 0.77, n = 66). It was found that this linear relation was valid not within one bone type alone. Linear regression analysis on the combined data of all bones demonstrated that all bones obeyed the same global linear relation between measured and the calculated torsional stiffness (r2 = 0.98, n = 142). This implies that one and the same beam model is valid for the different bone types investigated. The calculation of stiffness from resonant frequencies, however, requires total bone mass, m, and length to be known. In view of in vivo applications, the feasibility of using total bone mineral content (TBMC) as a measure for m was investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

In vitro analysis of urinary calculi: type differentiation using computed tomography and bone densitometry.

Thirty-six urinary stones were studied by computed tomography and bone densitometry in order to find a correlation between the chemical composition of the stones and the densitometric data. In vitro, the more common cases of lithiasis can be divided into 3 main groups: uric acid, cystine and the calcium salts, e.g. calcium oxalate monohydrate, calcium oxalate dihydrate and calcium phosphate. Struvite stones fall between the second and third groups. Computed tomography and bone densitometry can differentiate between the groups, provided that the value of the "stone mineral or calcium content" is correlated with the true calculated volume of the stone (resulting in the specific stone density) instead of the projection area (resulting in the area density). This is only possible in vitro. The in vivo application of these technologies in the treatment of stones of unknown composition could provide important information, but major restrictive factors pose difficulties. Further clinical studies are necessary, especially to define the role of bone densitometry.

Absorptiometry, Photon↗
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↗