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P Geusens

Publications and source records attributed to P Geusens.

At least 19 recordsLinked to original sources
PubMed2006

Hip and non-spine fracture risk reductions differ among antiresorptive agents: Evidence from randomised controlled trials.

A number of antiresorptive agents reduce the risk of vertebral fractures, but few have shown consistent effects on hip and other non-spine fractures. Meta-analysis provides a more precise estimate than individual trials when results are consistent across pooled trials. Earlier meta-analyses summarised the results for vertebral and non-spine fractures. New data have emerged for hormone therapy (HT), alendronate (ALN), risedronate (RIS) and ibandronate (IBN). We surveyed recent reports of randomised, placebo-controlled trials with non-spine and/or hip fracture data, and used meta-analysis where appropriate to test for heterogeneity and derive pooled estimates. The magnitude of effect on hip fracture appears to be similar to that for non-spine fracture for each drug, but differs among drugs. Based on the current data, ALN reduces the risk of hip and non-spine fracture by 49-55%, HT by 25-36% and RIS by 26-27%. There is insufficient and/or inconsistent evidence of an effect on these fractures for IBN, calcitonin and raloxifene.

Aged↗
PubMed2006

A simple clinical score for estimating the long-term risk of fracture in post-menopausal women.

BACKGROUND: Simple tools are needed to identify patients at high risk of fracture. AIM: To develop a simple clinical tool for assessing 5-year risk of fracture. DESIGN: Cohort study. METHODS: The study population consisted of all women aged 50+ included in the THIN Research Database (containing computerized medical records of UK general practices). Using Cox proportional hazards models, a risk score was initially estimated from age, body mass index, and clinical risk factors. The 5-year risk of fracture (survival function) was estimated for each score. RESULTS: The study population included 366 104 women aged > or = 50 years (mean follow-up 5.8 years). Of these, 6453 suffered a hip fracture. Several characteristics independently contributed to the fracture risk score (age, body mass index, fracture and fall history, previous diagnoses and use of medication). The 5-year risks for hip fracture for patients with total scores of 10, 30 and 50 were 0.3% (95%CI 0.3-0.4%), 2.2% (95%CI 2.1-2.2%), and 13.1% (95%CI 12.5-13.7%), respectively. A woman aged 65 years with low BMI and a history of both fracture and falling would have a hip fracture risk score of 37, with a corresponding 5-year risk for a hip fracture of 4.1% (4.0-4.2%). The risk score was validated and tested in another population (from GPRD), with a good concurrence between predicted and observed risks of fracture. DISCUSSION: This risk score predicts the long-term risk of fracture, and could be used for targeting patients for further investigation, such as bone densitometry.

Accidental Falls↗
PubMed2006

Individual fracture risk and the cost-effectiveness of bisphosphonates in patients using oral glucocorticoids.

OBJECTIVES: There are few data on the cost-effectiveness of bisphosphonates with oral glucocorticoids (GCs). An individual patient-based pharmaco-economic model was developed. METHODS: Data were obtained from a cohort of oral GC users aged 40+ (n = 190 000) in the UK General Practice Research Database. Individualized fracture and mortality risks were calculated specific for age, sex, daily and cumulative GC dose, indication and other clinical risk factors. UK costs of medication and direct costs of fracture were obtained from National Institute for Clinical Excellence and used to estimate costs per quality-adjusted life-year (QALY) gained and fracture prevented for bisphosphonates in patients treated for 5 yrs with GCs. RESULTS: With the use of 5 mg GCs daily, the cost per one QALY gained with bisphosphonates was 41k UK pounds (95% confidence intervals 22-72k) in women aged <60 [men 40k pounds (29-54k)], 17k pounds (13-24k) in women aged 60-79 [men 43k pounds (31-60k)], 5k pounds(3-6k) in women aged 80+ [men 35k pounds (25-46k)]. With 15 mg GC, these figures were 17k pounds (14-21k), 13k pounds (10-16k) and 15k pounds (9-26k) in women and 22k pounds (17-26k), 34 pounds (23-53k) and 33k pounds (27-42k) in men, respectively. When stratifying by overall fracture risk and life expectancy at the start of GC therapy, cost per QALY increased with decreasing life expectancy. Patients with rheumatoid arthritis had comparatively better cost-effectiveness, given higher fracture risk and better life expectancy. CONCLUSIONS: The cost-effectiveness of bisphosphonates varied substantially. Bisphosphonates can be considered cost-effective in patients with higher fracture risks, such as elderly patients (with a life expectancy over 5 yrs), and younger patients with a fracture history, low body mass index, rheumatoid arthritis or using high GC doses.

Adult↗
PubMed2006

A prospective randomised multicentre study comparing continuous and intermittent treatment with celecoxib in patients with osteoarthritis of the knee or hip.

OBJECTIVE: To compare the effects of continuous and intermittent celecoxib treatment in patients with knee or hip osteoarthritis in flare. METHODS: In this 24-week, prospective, randomised, double-blind, placebo-controlled study, patients were randomly assigned to receive continuous (n = 62) or intermittent (n = 61) treatment with celecoxib 200 mg once daily. The primary efficacy end point was the area under the curve (AUC) of the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores between baseline and week 24 divided by the time interval. Secondary end points included the percentage of days with intake of the flare drug, the AUC of the change in the WOMAC total scores, the mean change from baseline in the WOMAC scores, and the patient's and physician's global assessment of osteoarthritis. RESULTS: There were no significant differences between patients randomised to continuous or intermittent treatment in the primary end point or most of the secondary end points, although a consistent trend supporting continuous treatment was observed. The percentage of days with intake of the flare drug was significantly lower (p = 0.031) in the group receiving continuous versus intermittent celecoxib. Both treatment regimens were well tolerated. CONCLUSION: The results of this pilot study indicate a potential clinical difference between continuous and intermittent treatment with celecoxib, and may be useful in designing future trials. A larger trial on both efficacy and safety outcomes is required for conclusive evidence in favour of either continuous or intermittent treatment.

Aged↗
PubMed2006

Partial prevention of long-term femoral bone loss in aged ovariectomized rats supplemented with choline-stabilized orthosilicic acid.

Silicon (Si) deficiency in animals results in bone defects. Choline-stabilized orthosilicic acid (ch-OSA) was found to have a high bioavailability compared to other Si supplements. The effect of ch-OSA supplementation was investigated on bone loss in aged ovariectomized (OVX) rats. Female Wistar rats (n = 58, age 9 months) were randomized in three groups. One group was sham-operated (sham, n = 21), and bilateral OVX was performed in the other two groups. OVX rats were supplemented orally with ch-OSA over 30 weeks (OVX1, n = 20; 1 mg Si/kg body weight daily) or used as controls (OVX0, n = 17). The serum Si concentration and the 24-hour urinary Si excretion of supplemented OVX rats was significantly higher compared to sham and OVX controls. Supplementation with ch-OSA significantly but partially reversed the decrease in Ca excretion, which was observed after OVX. The increase in bone turnover in OVX rats tended to be reduced by ch-OSA supplementation. ch-OSA supplementation increased significantly the femoral bone mineral content (BMC) in the distal region and total femoral BMC in OVX rats, whereas lumbar BMC was marginally increased. Femoral BMD was significantly increased at two sites in the distal region in OVX rats supplemented with ch-OSA compared to OVX controls. Total lumbar bone mineral density was marginally increased by ch-OSA supplementation. In conclusion, ch-OSA supplementation partially prevents femoral bone loss in the aged OVX rat model.

Absorptiometry, Photon↗
PubMed2006

Positive effect of alendronate on bone mineral density and markers of bone turnover in patients with rheumatoid arthritis on chronic treatment with low-dose prednisone: a randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Alendronate has been described to have a bone-sparing effect in patients treated with moderate and high dosages of prednisone for heterogeneous diseases, however no data are available on groups of patients with the same underlying diseases who receive chronic low-dose prednisone treatment. The objective of the investigation reported here was, therefore, to study the effect of alendronate on bone mineral density (BMD) of the lumbar spine and hips in patients with rheumatoid arthritis (RA) who are on chronic low-dose prednisone treatment. METHODS: A total of 163 patients with RA, according to the ACR-criteria, were enrolled in a double-blind, placebo-controlled trial. The patients were treated with low-dose prednisone (<or=10 mg/day) for at least 3 months. The patients were randomized to receive daily doses of alendronate or placebo: men and premenopausal women received 5 mg alendronate (or placebo) daily; postmenopausal women received 10 mg alendronate (or placebo) daily. All patients received daily calcium (500 mg, or 1000 mg, depending on baseline dietary calcium intake) and vitamin D3 (400 IU) supplementation. BMD of the lumbar spine (L1-L4) and the (total) hip was measured at baseline and after 6 and 12 months. The primary endpoint was change in BMD of the lumbar spine after 12 months (ITT). At baseline and after 3 and 12 months, serum bone-specific alkaline phosphatase (BAP) and urinary excretion of N-telopeptide (NTX) were measured. Radiographs of the thoracic and lumbar spine were made at baseline and after 12 months and subsequently scored for vertebral deformities. RESULTS: The groups were comparable at baseline in age, gender, daily dosage of prednisone, BMD at the spine and the hip and markers of bone turnover, while the number of patients with prevalent vertebral deformities was slightly higher in the alendronate-treated patients (54% versus 39%, not significant). After 12 months, BMD at the lumbar spine had increased by 3.7% in the alendronate-treated patients and decreased by -1.0% in the placebo-treated patients (p<0.0001); at the hip, the changes were +1.0% and -0.1%, respectively (not significant). After 3 months, serum BAP had decreased by 16.9% in the alendronate group versus 3.3% in the placebo group (p=0.0005), while urinary NTX had decreased by 46.4% in the alendronate group versus 12.1% in the placebo group (p<0.0001). After 12 months, no statistically significant difference was found between the groups with respect to number of patients with incident vertebral or non-vertebral fractures. Adverse effects were relatively common in these patients with severe RA: adverse effects were observed in 68% of the alendronate-treated patients and in 73% of the placebo patients (not significant), while serious adverse events were observed in 13% and 17%, respectively (not significant). CONCLUSION: We observed a favourable effect of alendronate on the BMD of the lumbar spine and on the markers of bone turnover in patients with RA treated with low-dose prednisone. These data support the conclusion that the prescribing of alendronate is not only beneficial in patients treated with high-dose prednisone but also in RA patients chronically treated with low-dose prednisone.

Absorptiometry, Photon↗
PubMed2006

Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis.

OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) have an increased risk of fracture, and to estimate their long-term absolute fracture risk. METHODS: We studied patients with RA ages >or=40 years in the British General Practice Research Database, each matched by age, sex, calendar time, and practice to 3 control patients. Incident fractures, as recorded in the computerized medical records, were ascertained over a median followup of 7.6 years. The fracture rate in RA patients compared with controls was adjusted for smoking, body mass index (BMI), and several clinical risk factors, and Cox proportional hazards models were used to calculate the relative risk (RR) of fracture in RA. A risk score was then developed to provide an estimate of the 5- and 10-year fracture risk among RA patients. RESULTS: There were 30,262 patients with RA, of whom 2,460 experienced a fracture during followup. Compared with controls, patients with RA had an increased risk of fracture, which was most marked at the hip (RR 2.0, 95% confidence interval [95% CI] 1.8-2.3) and spine (RR 2.4, 95% CI 2.0-2.8). Indicators of a substantially elevated risk of fracture (at the hip) included >10 years' duration of RA (RR 3.4, 95% CI 3.0-3.9), low BMI (RR 3.9, 95% CI 3.1-4.9), and use of oral glucocorticoids (RR 3.4, 95% CI 3.0-4.0). Modeling of the long-term risk profiles revealed that, for example, in a woman age 65 years with longstanding RA whose risk factors also included low BMI, a history of fracture, and frequent use of oral glucocorticoids, the 5-year risk of hip fracture was 5.7% (95% CI 5.3-6.1%). CONCLUSION: Patients with RA are at increased risk of osteoporotic fractures. This increased risk is attributable to a combination of disease activity and use of oral glucocorticoids.

Adult↗
PubMed2005

Determinants of hyperkyphosis in patients with ankylosing spondylitis.

OBJECTIVE: To determine clinical and radiographic determinants of hyperkyphosis in patients with ankylosing spondylitis. METHODS: Spinal hyperkyphosis was assessed by occiput to wall distance (OWD) in 135 patients participating in the OASIS cohort and defined as OWD >0. Disease activity was assessed by the Bath ankylosing spondylitis disease activity index (BASDAI). Wedging of the vertebrae was calculated as the Ha/Hp ratio. Structural damage of the spine was assessed by the modified Stoke ankylosing spondylitis spine score (mSASSS). Hip involvement was assessed by the Bath ankylosing spondylitis radiology index (BASRI) and defined as a score >2. Data were analysed by multiple regression analysis on van der Waerden-normal OWD values, with mean Ha/Hp ratio, mSASSS, hip involvement, and BASDAI as explanatory variables, and age, sex, and disease duration after diagnosis as covariates. RESULTS: 61 patients (45.2%) had an OWD >0 cm. Of these, 81% were male, v 57% in the group with normal OWD (p<0.001). Forty two patients had wedged thoracic vertebrae, and 27 of these (44%) had an increased OWD, compared with 15 of 74 with a normal OWD (20%) (p = 0.005). OWD was correlated with mean wedging of the thoracic spine (r = -0.45, p = 0.01), mSASSS (r = 0.56, p = 0.01), and hip involvement (r = 0.2, p = 0.05). Multivariate analysis showed that mSASSS (standardised beta (stbeta) = 0.52; p<0.001), wedging of the thoracic spine (stbeta = -0.28; p = 0.01), and BASDAI (stbeta = 0.15; p = 0.05) were independent determinants of OWD. CONCLUSIONS: Radiological damage of the cervical and lumbar spine, thoracic wedging, and disease activity are determinants of hyperkyphosis in patients with ankylosing spondylitis. These findings could be important in determining treatment goals in this disease.

Adult↗
PubMed2005

Arthritis instantaneously causes collagen type I and type II degradation in patients with early rheumatoid arthritis: a longitudinal analysis.

BACKGROUND: Markers of collagen type I (CTX-1) and type II (CTX-II) degradation, reflecting bone and cartilage breakdown, appear to predict long term radiographic progression in chronic persistent arthritis. OBJECTIVE: To analyse longitudinally whether changes in arthritis severity are linked to immediate changes in the level of CTX-I and CTX-II degradation. METHODS: CTX-I and CTX-II were measured in urine samples from 105 patients with early rheumatoid arthritis who had participated in the COBRA trial at baseline and at 3, 6, 9, and 12 months after the start of treatment. The course of the biomarkers over time was compared with the course of ESR, swollen and tender joint counts, and 28 joint disease activity score (DAS28), measured at the same time points, with adjustment for rheumatoid factor, treatment, and baseline radiographic damage, by generalised estimating equations (GEE) with first order autoregression. RESULTS: GEE showed that CTX-I was longitudinally associated with DAS28, but not with ESR, swollen joint count, or tender joint count. CTX-II, however, was longitudinally associated with ESR, swollen joint count and DAS28, but not with tender joint count. The longitudinal association implies that an increase in the extent of arthritis is immediately followed by an increase in collagen type II degradation, and to a lesser extent collagen type I degradation. CONCLUSIONS: Cartilage degradation as measured by CTX-II and to a lesser extent bone degradation as measured by CTX-I closely follows indices of arthritis. Clinically perceptible arthritis is responsible for immediate damage, which will become visible on plain x rays only much later.

Adult↗
PubMed2005

Osteoporosis therapy: an example of putting evidence-based medicine into clinical practice.

A major aim of evidence-based medicine is to assist clinical decision-making by providing the most current and reliable medical information. Systematic reviews and meta-analyses are important tools in this process. Systematic reviews identify and compile relevant evidence, while meta-analyses summarize and quantify the results of such reviews. Results from meta-analyses are, at present, the main source of summary evidence for the efficacy of treatments for a specific condition. They are important tools for helping to choose among treatment options, although they cannot be used to directly compare the magnitude of the effect of various therapies. However, the methods used and the consequent clinical value of the results, may be poorly understood by clinicians, who may therefore not take full advantage of the evidence. Recently, a panel of experts in osteoporosis and evidence-based medicine applied rigorous, validated, scientific standards to produce a systematic review and meta-analysis of randomized controlled trials of anti-resorptive agents used to treat osteoporosis. They found that, although several agents reduced the risk of vertebral fracture, only two, alendronate and risedronate, demonstrated convincing evidence for both non-vertebral and vertebral fracture risk reductions. The clinical implication of these results is that there are important differences in anti-fracture efficacy among currently available agents. In the absence of evidence from head-to-head clinical trials and because of the systematic nature and methodological rigor of the analyses, these data provide important information for clinical decision-making.

Aged↗
PubMed2005

A simple score for estimating the long-term risk of fracture in patients using oral glucocorticoids.

BACKGROUND: Previous analyses of risk factors for glucocorticoid (GC)-induced osteoporosis have focused on the estimation of relative rather than absolute fracture probability. AIM: To estimate risk scores for the individual probability of fracture in GC users. DESIGN: Retrospective data analysis. METHODS: We evaluated all patients aged 40 years or older with a prescription for oral GCs in the General Practice Research Database (GPRD), which comprises the computerized medical records of around 7 million UK subjects. Individual risk factors for osteoporotic fractures were identified, and combined in a predictive model for 10-year absolute fracture risk. RESULTS: Of 191 752 oral GC users aged > or =40 years, 7412 experienced an osteoporotic fracture. Several characteristics independently contributed to the fracture risk score (GC therapy, age, gender, fall history, fracture history, body mass index, smoking, previous diagnoses, use of medication, recent hospitalization and indication for GC treatment). Scores of 30, 40 and 50 corresponded to absolute 5-year fracture risks of 6.2%, 15.3% and 35.2%, respectively. A woman aged 65 years with RA, low BMI, and a previous history of fracture and falls, who used 15 mg GC daily (total risk score 54) would have a 5-year fracture risk of 47% (a man with similar history, 30.1%). Short-term use of high-dose GC therapy (> or =30 mg) was associated with only a small increased risk of osteoporotic fracture (RR 1.21, 95%CI 1.04-1.42) in patients with a history of GC use. DISCUSSION: This risk score helps to predict an individual's risk of fracture during GC use. Decisions about bone protection treatment could be based on long-term risks of fracture.

Accidental Falls↗
PubMed2004

Alendronate produces greater effects than raloxifene on bone density and bone turnover in postmenopausal women with low bone density: results of EFFECT (Efficacy of FOSAMAX versus EVISTA Comparison Trial) International.

OBJECTIVES: Alendronate and raloxifene are antiresorptive agents with different mechanisms of action, each used to treat osteoporosis in postmenopausal women. This study was undertaken to compare the efficacy and tolerability of alendronate to raloxifene in postmenopausal women with low-bone density. DESIGN: Randomized, double-masked, double-dummy multicentre international study. SETTING: Clinical trial centres in Europe, South America and Asia-Pacific. SUBJECTS: A total of 487 postmenopausal women with low bone density, based on bone mineral density (BMD) of the lumbar spine or hip (T-score < or =-2.0). Interventions. Patients received either alendronate 70 mg once weekly and daily placebo identical to raloxifene or raloxifene 60 mg daily and weekly placebo identical to alendronate for 12 months. MAIN OUTCOME MEASURES: Evaluations included BMD of the lumbar spine and hip and markers of bone turnover at 6 and 12 months and adverse event reporting. RESULTS: Alendronate demonstrated substantially greater increases in BMD than raloxifene at both lumbar spine and hip sites at 12 months. Lumbar spine BMD increased 4.8% with alendronate vs. 2.2% with raloxifene (P < 0.001). The increase in total hip BMD was 2.3% with alendronate vs. 0.8% with raloxifene (P < 0.001). Reductions in bone turnover were significantly larger with alendronate than raloxifene. Overall tolerability was similar, however, the proportion of patients reporting vasomotor events was significantly higher with raloxifene (9.5%) than with alendronate (3.7%, P = 0.010). The proportion of patients reporting gastrointestinal events was similar between groups. CONCLUSION: In postmenopausal women with low bone density, improvements in BMD and markers of bone turnover were substantially greater during treatment with alendronate compared to raloxifene.

Alendronate↗
PubMed2004

Efficacy, safety and tolerability of lumiracoxib in patients with rheumatoid arthritis.

A randomised, double-blind study was performed to assess the efficacy and tolerability of lumiracoxib in patients with rheumatoid arthritis (RA). Patients received lumiracoxib 200mg once daily (o.d.) (n= 280), lumiracoxib 400mg o.d. (n= 281), naproxen 500 mg twice daily (n= 279) or placebo (n= 284) for 26 weeks. The primary efficacy variable was response to treatment according to ACR20 criteria (adjusted for prohibited concomitant or excessive rescue medication use and discontinuations due to unsatisfactory therapeutic response) at week 13. Safety and tolerability was also assessed. Significantly more patients receiving lumiracoxib than placebo were responders according to ACR20 criteria at week 13 (41.1 and 42.7% for lumiracoxib 200 and 400 mg o.d., respectively; 32.4% for placebo; both p < 0.05). The proportion responding to naproxen (39.1%) was not significantly different from placebo. Prespecified gastrointestinal adverse events were more frequent with naproxen than with either lumiracoxib dose or placebo. Lumiracoxib is therefore an effective and well-tolerated therapy for RA.

Adult↗
PubMed2003

Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age.

Although several observational studies have demonstrated an association between vitamin K status and bone mineral density (BMD) in postmenopausal women, no placebo-controlled intervention trials of the effect of vitamin K1 supplementation on bone loss have been reported thus far. In the trial presented here we have investigated the potential complementary effect of vitamin K1 (1 mg/day) and a mineral + vitamin D supplement (8 microg/day) on postmenopausal bone loss. The design of our study was a randomized, double-blind, placebo-controlled intervention study; 181 healthy postmenopausal women between 50 and 60 years old were recruited, 155 of whom completed the study. During the 3-year treatment period, participants received a daily supplement containing either placebo, or calcium, magnesium, zinc, and vitamin D (MD group), or the same formulation with additional vitamin K1 (MDK group). The main outcome was the change in BMD of the femoral neck and lumbar spine after 3 years, as measured by DXA. The group receiving the supplement containing additional vitamin K1 showed reduced bone loss of the femoral neck: after 3 years the difference between the MDK and the placebo group was 1.7% (95% Cl: 0.35-3.44) and that between the MDK and MD group was 1.3% (95% Cl: 0.10-3.41). No significant differences were observed among the three groups with respect to change of BMD at the site of the lumbar spine. If co-administered with minerals and vitamin D, vitamin K1 may substantially contribute to reducing postmenopausal bone loss at the site of the femoral neck.

Absorptiometry, Photon↗