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Biomedical subjects

W F Lems

Publications and source records attributed to W F Lems.

At least 55 records · Page 3Linked to original sources

Data driven attempt to create a clinical algorithm for identification of women with rheumatoid arthritis at high risk of osteoporosis.

OBJECTIVES: To examine relations between osteoporosis and low bone mass and demographic and clinical variables in patients with rheumatoid arthritis (RA), in an attempt to develop a data driven clinical tool for identification of patients at high risk of osteoporosis. METHODS: All patients were recruited from a county based register and were examined cross sectionally with a variety of clinical and health status measures as well as bone density measures (anteroposterior spine L2-4, total hip, and femoral neck). Associations between osteoporosis (T score < or = -2.5SD) and low bone mass (T score < or = -1SD), on the one hand, and demographic and clinical measures, on the other, were examined bivariately and by logistic regression analyses. RESULTS: 394 patients with a mean age of 54.8 years were examined. The percentages having osteoporosis/low bone mass were 16.8/45.8, 14.7/54.5 and 14.7/55.5 in spine L2-4, total hip, and femoral neck, respectively. Osteoporosis and low bone mass were bivariately related to age, body mass index (BMI), disease duration, disease process measures, presence of deformed joints, physical disability, current use of corticosteroids, and history of non-vertebral fracture. In multivariate analyses, age >60 years, low BMI, and current use of corticosteroids were consistently related to osteoporosis and to low bone mass at all sites. The presence of deformed joints was associated with osteoporosis at the total hip, and a history of previous non-vertebral fracture with osteoporosis at the femoral neck. The Modified Health Assessment Questionnaire (MHAQ) > or = 1.5 and non-vertebral fracture were also independently associated with low bone mass at the hip. The logistic regression analyses models could, however, only predict osteoporosis with a sensitivity of about 50-60% and a specificity of 80-90% at the various measurement sites, and low bone mass with a sensitivity and specificity of about 70%. CONCLUSION: Consideration of demographic and disease markers may be of some help in predicting presence of osteoporosis or low bone mass, but a combination of markers cannot be used as a clinical tool with sufficient sensitivity and specificity for the identification of osteoporosis or low bone mass in patients with RA.

Activities of Daily Living↗

[Effectiveness, safety, and costs of measures for prevention of gastropathy due to the use of nonsteroidal antiinflammatory drugs].

NSAID gastropathy, because of its severity and prevalence, is the most important side effect of nonsteroidal anti-inflammatory drugs. Protective strategies are advocated in patients with high risk for NSAID gastropathy (age over 60 years and/or previous ulcer). Different strategies for the prevention of NSAID gastropathy are: using a cyclo-oxygenase (COX)-2 inhibitor, adding a prostaglandin analogue, an H2-receptor antagonist or a proton pump inhibitor or eradicating Helicobacter pylori. On the basis of efficacy, safety and costs prescription of a proton pump inhibitor as a prophylactic agent appears to be the best option; prescription of a prostaglandin analogue is a good alternative. The preliminary data on the COX-2 inhibitors are promising. The role of H. pylori in NSAID gastropathy is not yet elucidated.

Anti-Inflammatory Agents, Non-Steroidal↗

[Pharmacological prevention of osteoporosis in patients on corticosteroid medication].

Twenty-five per cent of the patients using corticosteroids for long periods of time develops at least one fracture. Corticosteroids lead to osteoporosis through increase of renal calcium excretion and decrease of intestinal calcium absorption, bone formation by osteoblasts and serum levels of sex hormones. In spite of guidelines according to which patients protractedly using corticosteroids should take sufficient calcium and cholecalciferol, only about one-tenth of them takes any form of medication to prevent osteoporosis. It seems advisable to prescribe additional anti-osteoporosis medication for patients using > or = 7.5 mg prednisone during at least 3 months and who have a low mineral density of bone; only of biphosphonates a preventive effect clearly has been demonstrated. For postmenopausal women, hormonal supplementation therapy may offer additional benefit, reducing the risk of cardiovascular disease.

Adrenal Cortex Hormones↗

Effect of low-dose prednisone (with calcium and calcitriol supplementation) on calcium and bone metabolism in healthy volunteers.

The administration of moderate to high doses of corticosteroids is associated with bone loss. This probably results from the uncoupling of bone formation (decreased) and bone resorption (unchanged or increased). We examined the effect of low-dose (10 mg/day) prednisone (LDP) and the possible mitigating effects of calcium and 1.25 (OH)2 vitamin D (calcitriol) on calcium and bone metabolism in eight healthy, young male volunteers. The study consisted of four observation periods: in the first period, LDP was prescribed during 1 week; in the second, third and fourth periods, calcium (500 mg/day), calcitriol (0.5 micrograms b.i.d.) and calcium in combination with calcitriol, respectively, were added to LDP. Bone formation was measured by means of serum osteocalcin, carboxy-terminal propeptide of type 1 procollagen (P1CP) and alkaline phosphatase, bone resorption by means of urinary excretion of calcium, hydroxyproline, (free and total) pyridinoline, (free and total) deoxypyridinoline and serum carboxy-terminal cross-linked telopeptide of type 1 collagen (1CTP). Dietary calcium and sodium intake were maintained at a stable level during the entire study period. Treatment with LDP led to a decrease in osteocalcin, P1CP and alkaline phosphatase (all P < 0.01). Urinary excretion of pyridinolines, hydroxyproline and serum 1CTP did not increase, but remained unchanged or slightly reduced (P < 0.05), depending on the time of measurement and the marker of bone resorption. Parathyroid hormone (PTH) (insignificantly) increased during LDP (+19%) and LDP plus calcium (+14%), but decreased during supplementation with calcitriol (-16%) and calcium/calcitriol (-44%; P < 0.01). Urinary excretion of calcium increased during treatment with LDP and calcitriol (P < 0.05) and calcium/calcitriol (P < 0.05). It is concluded that LDP has a negative effect on bone metabolism, since bone formation decreased while bone resorption remained unchanged or decreased slightly. The increase in PTH during LDP could be prevented by calcitriol combined with calcium supplementation.

Adult↗

Effect of sodium fluoride on the prevention of corticosteroid-induced osteoporosis.

To investigate whether sodium fluoride (NaF) is able to prevent bone loss in patients treated with corticosteroids (Cs), we performed a randomized double-masked, placebo-controlled trial with 44 Cs-treated patients without established osteoporosis, defined as the absence of previous peripheral fractures and vertebral deformities on radiographs. The effects of NaF (25 mg twice daily) and placebo on the bone mineral density (BMD) of the lumbar spine and hips were compared at baseline and at 6, 12, 18 and 24 months. After 2 years, the BMD of the lumbar spine had decreased in the placebo group by 3.0% (95% CI: -4.9% to -1.0%; p < 0.01); in the NaF group there was a statistically insignificant increase in BMD of 2.2% (95% CI: -0.8% to +5.3%). The difference in the changes in BMD between the two groups was +5.2% (95% CI: +1.8% to +8.6%; p < 0.01). In the hips, BMD had decreased after 2 years in both groups: in the placebo group by -3.0% (95% CI: -5.0% to -1.0%; p < 0.05) and in the NaF group by 3.8% (95% CI: -6.1% to -1.5%; p < 0.01). The difference in the changes in BMD between the two groups was not significant: +0.8% (95% CI: -2.1% to +3.8%). Three vertebral deformities were observed in the placebo group and one in the NaF group (insignificant difference), while no peripheral fractures occurred during the study period. It is concluded that in Cs-treated patients without established osteoporosis NaF prevents bone loss in the lumbar spine but does not have a positive effect on the BMD of the hips.

Adrenal Cortex Hormones↗

Methods to score vertebral deformities in patients with rheumatoid arthritis.

The objective was to compare four different scoring methods for vertebral deformities: the semiquantitative Kleerekoper score and three quantitative scores (according to Minne, Melton and Raymakers) in patients with rheumatoid arthritis (RA). Lateral radiographs of the thoracic and lumbar vertebral column were scored in 52 RA patients treated with corticosteroids (Cs) and 52 RA patients not Cs treated (matched for age and gender). Clinically manifest vertebral fractures were defined as a vertebral deformity leading to the prescription of therapy: bedrest and/or analgesies. The number of Cs-treated RA patients with vertebral deformities was only increased according to the Kleerekoper score (relative risk 2.31; 95% confidence interval 1.36-3.90). The total number of vertebral deformities was increased in Cs-treated RA patients according to the method of Kleerekoper. Minne and Raymakers, but not according to Melton. The Spinal Deformity Index was increased in the Cs-treated RA patients according to Minne (P < 0.05), but not according to Raymakers. In both patient groups, the number of patients with clinically manifest vertebral fractures was much lower than that of vertebral deformities, e.g. in the Cs-treated patients 13% vs 35.79% (depending on the scoring method used). All eight patients with clinically manifest vertebral fractures had severe height loss (25% or more) in at least one vertebra. Vertebral deformities seem to occur more often in Cs-treated patients than in those not Cs-treated. However, differences exist in the number of patients with vertebral deformities and in the total number of vertebral deformities between different scoring methods. This emphasizes the need for a gold standard or consensus for defining vertebral deformities, in which, in our opinion, a Spinal Deformity Index has to be included. Clinically manifest vertebral fractures are predominantly characterized by severe vertebral deformities on X-rays.

Aged↗

Is addition of sodium fluoride to cyclical etidronate beneficial in the treatment of corticosteroid induced osteoporosis?

OBJECTIVE: To investigate whether administration of sodium fluoride (NaF) in addition to cyclical etidronate has a positive effect on bone mineral density (BMD) in patients with established osteoporosis during continued treatment with corticosteroids. PATIENTS AND METHODS: 47 patients who were receiving treatment with corticosteroids were included in a two year randomised, double blind, placebo controlled trial. Established osteoporosis was defined as a history of a peripheral fracture or a vertebral deformity, or both, on a radiograph. All patients were treated with cyclical etidronate, calcium, and either NaF (25 twice daily) or placebo. Vitamin D was supplemented in the case of a low serum 25 (OH) vitamin D concentration. BMD of the lumbar spine and hips was measured at baseline and at 6, 12, 18, and 24 months. RESULTS: After two years of treatment, the BMD of the lumbar spine in the etidronate/NaF group had increased by +9.3% (95% confidence intervals (CI): +2.3% to +16.2%, p < 0.01), while the BMD in the etidronate/placebo group was unchanged: +0.3% (95% CI: -2.2% to +2.8%). The difference in the change in BMD between groups was +8.9% (95% CI: +1.9% to +16.0%, p < 0.01). For the hips, no significant changes in BMD were observed in the etidronate/NaF group after two years: -2.5% (95% CI: -6.8% to +1.8%); in the etidronate/placebo group BMD had significantly decreased: -4.0% (95% CI: -6.6% to -1.4%; p < 0.01). The difference between the groups was not significant: +1.5% (95% CI: -3.4% to +6.4%). No significant differences in number of vertebral deformities and peripheral fractures were observed between the two groups. CONCLUSION: The effect of combination treatment with NaF and etidronate on the BMD of the lumbar spine in corticosteroid treated patients with established osteoporosis is superior to that of etidronate alone.

Adult↗

Changes in (markers of) bone metabolism during high dose corticosteroid pulse treatment in patients with rheumatoid arthritis.

OBJECTIVE: To examine the effect of high dose corticosteroid pulse treatment (three times 200 mg dexamethasone intravenously in eight days) on calcium and bone metabolism in 17 consecutive patients with active rheumatoid arthritis (RA). METHODS: Bone formation was quantified by measurement of serum alkaline phosphatase, osteocalcin, and carboxyterminal propeptide of type I procollagen (pro-I-CPP) concentrations. Bone resorption was measured by urinary excretion of calcium, hydroxyproline, (free and total) deoxypyridinoline (Dpyr), (free and total) pyridinoline (Pyr), and serum concentrations of the carboxyterminal cross linked telopeptide of type I collagen (I-CTP). Disease activity of RA was measured by erythrocyte sedimentation rate, C reactive protein, and Ritchie and Thompson joint scores. RESULTS: Disease activity was initially high, and decreased during corticosteroid pulse treatment and the following five weeks. Osteocalcin, alkaline phosphatase, and pro-I-CPP concentrations were initially within normal limits, while I-CTP, Dpyr, and Pyr were increased. Osteocalcin and pro-I-CPP concentrations decreased (p < 0.01) during corticosteroid pulse treatment, but rapidly returned to baseline after the treatment. No changes were observed in alkaline phosphatase and urinary excretion of calcium and hydroxyproline. Bone resorption measured by serum I-CTP and urinary excretion of Pyr and Dpyr was unchanged or decreased (p < 0.05-0.01), depending on the time of measurement and the parameter measured. CONCLUSIONS: In these patients with active RA, bone resorption was increased, while bone formation was within normal limits. During high dose corticosteroid pulse treatment, bone formation was only transiently decreased, while markers of bone resorption were unchanged or decreased. Because corticosteroid pulse treatment has only a short term negative effect on bone formation, and because it probably reduces bone resorption, at least partly as a result of the decreased disease activity, the effect of corticosteroid pulse treatment on bone may be assumed to be relatively mild.

Acute Disease↗

Changes in calcium and bone metabolism during treatment with low dose prednisone in young, healthy, male volunteers.

The effect of low dose prednisone on calcium and bone metabolism was evaluated in 8 healthy, young, male volunteers. Sodium and calcium intake were kept stable during the whole study period of 7 weeks. Week 0 was the baseline period; during week 1, 3 and 5 prednisone (10 mg/day) was given, during week 3 together with 500 mg elementary calcium and during week 5 with 4000 IU vitamin D on alternate days. During week 2, 4 and 6 no medication was given. No changes occurred in fasting urinary excretion of calcium or hydroxyproline, nor in serum levels of alkaline phosphatase, 25-Vitamin D, PTH, creatinine and inorganic phosphorus. A rapid decrease of serum osteocalcin during prednisone intake was found (p<0.01). This dip also occurred during prednisone and vitamin D treatment, but did not occur when calcium was added to prednisone, although the baseline value was lower at the start of combined treatment with prednisone and calcium. Serum calcium decreased during prednisone (p<0.05), but when prednisone was given together with calcium, an increase of serum calcium was found (p< 0.05). It is concluded that 10 mg prednisone/day decreases bone formation, as shown by its effect on osteocalcin, while no influence is seen on bone resorption. Thus, prednisone, even when used in low doses, influences bone metabolism by uncoupling bone formation (decreased) and bone resorption (unchanged). These data suggest that the Cs-associated decrease in serum osteocalcin and in serum calcium does not occur during calcium suppletion.

Adult↗

Local muscle hypertrophy due to an arterio-venous malformation.

A 20-yr-old man with progressive, painful diffuse swelling of his right shoulder muscles is reported. The diagnosis was muscle hypertrophy secondary to a congenital arterio-venous malformation (CAVM). Since a CAVM is not infrequently asymptomatic until the age of 20 to 30 yr and develops insidiously, the diagnosis may be delayed. In our patient, MRI rather than ultrasound and CT, led to the final diagnosis.

Adult↗

Transient decrease in osteocalcin and markers of type 1 collagen turnover during high-dose corticosteroid pulse therapy in rheumatoid arthritis.

The effect of corticosteroid pulse therapy on bone metabolism was studied in 10 patients with active RA. We measured alkaline phosphatase, osteocalcin and two recently introduced markers of collagen type 1 metabolism, reflecting synthesis (PICP) and degradation (ICTP). The day after the pulse therapy, there was a statistically significant (P < 0.05) decrease in osteocalcin, PICP and ICTP from the value at start. Three weeks after pulse therapy, these values had returned to baseline. During pulse treatment there is a transient decrease in bone formation, as shown by the changes in osteocalcin and PICP. Because of the changes in ICTP, we conclude that bone resorption is transiently reduced as well, but whether these changes result from a direct or an indirect effect on bone is not clear. ICTP has to be investigated further as a (serum) marker of bone resorption.

Aged↗

Adjuvant oestrogen treatment increases bone mineral density in postmenopausal women with rheumatoid arthritis.

OBJECTIVES: The beneficial effect of oestrogens on bone mineral density in women with osteoporosis is well known. Patients with rheumatoid arthritis (RA) are at risk for osteoporosis. A study was therefore set up to investigate the effects of adjuvant oestrogen treatment on bone metabolism and bone mineral density in postmenopausal women with RA. METHODS: Forty postmenopausal women with active RA were admitted to a placebo controlled, double blind study investigating the beneficial effect of adjuvant oestradiols or placebo on bone metabolism and bone mineral density. Thirty three patients completed 52 weeks of treatment. RESULTS: At the start both treatment groups were comparable for all parameters. In the oestrogen group serum concentrations of osteocalcin decreased and concentrations of sex hormone binding globulin increased during the study. Bone mineral density measured by dual energy x ray absorptiometry increased significantly in the lumbar vertebral spine and femoral neck in the oestrogen group compared with the placebo group. CONCLUSIONS: This study shows that the use of adjuvant oestrogens in post-menopausal women with active RA increases bone mineral density.

Aged↗