Effects of clodronate on vertebral fracture risk in osteoporosis: a 1-year interim analysis

McCloskey, Eugène; Selby, Peter L.; Takats, D. de; Bernard, J.; Davies, M.; Robinson, J. Elliott; Francis, Roger M.; Adams, Judith E.; Pande, Ketan C; Benéton, M. N. C.; Jalava, Taina; Löyttyniemi, Eliisa; Kanis, John А.

doi:10.1016/s8756-3282(00)00437-3

Cited by 43 publications

(19 citation statements)

References 27 publications

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“…Of importance may be the fact that we selected our subjects to have at least osteopenia in the lumbar spine whereas the participants in the abovementioned three studies were either unselected [8,10] or it was ensured that few women who entered the study had osteoporosis [9]. Note that in another study [19] in women with osteoporosis who were approximately 15 years older, 800 mg clodronate daily for 1 year was associated with a significant increase in total hip BMD of 1.3% compared with a decrease of 0.4% in the placebo group. The divergent results in these two studies might be explained by the rather small number of subjects in the 800 mg clodronate group in the present study or by clodronate's capability of better meeting slower bone turnover rate in late versus early postmenopausal women.…”

Section: Discussionmentioning

confidence: 99%

Prevention of Bone Loss by Clodronate in Early Postmenopausal Women with Vertebral Osteopenia: A Dose-Finding Study

Välimäki

Laitinen

Patronen³

et al. 2002

Osteoporosis International

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This double-masked, placebo-controlled study was undertaken to determine the efficacy and safety of oral clodronate in the prevention of bone loss in early postmenopausal women with vertebral osteopenia. Altogether 610 women with a mean age of 53 years were recruited for the study. They were 1-5 years postmenopausal and their lumbar spine bone mineral density (BMD) was at least 1 standard deviation below the mean of premenopausal women ( T-score < or =-1). The subjects were randomized into five study groups to receive either placebo, clodronate 65 mg, 400 mg or 800 mg daily, or intermittent clodronate in 3 month cycles with 400 mg daily for 15 days followed with no treatment for 75 days for 3 years. One hundred and eighty-seven of 509 women who completed the primary study continued in the extension study of 2 years in which previous placebo users were switched to clodronate 800 mg daily, while previous users of 400 mg or 800 mg of clodronate used either placebo or 800 mg of clodronate daily. In the primary study clodronate was administered in the evening, and in the extension 1 h before breakfast on an empty stomach. In the primary study mean changes in lumbar spine BMD were -3.4% in the placebo group and +0.4% in 800 mg clodronate group [difference between groups at 3 years 3.8% (95% CI 2.7% to 4.9%, p<0.0001)], and in the trochanter area BMD -1.1% in the placebo group, and + 0.4% in the 800 mg clodronate group [difference between groups at 3 years 1.5% (95% CI 0.05% to 2.9%)]. During the extension study mean changes in lumbar spine BMD were +1.5% in the clodronate group and -0.2 % in the placebo group [difference between groups 1.7% (CI 0.4% to 3.0%, p = 0.010)] and in trochanter BMD were +2.5% in the clodronate group and no change in the placebo group [difference between groups 2.1% (CI 0.3% to 3.9%, p = 0.007)]. No statistically significant differences between the placebo and 800 mg clodronate groups were found in the femoral neck BMD. In the primary study the urinary excretion of type I collagen aminoterminal telopeptide (NTX) decreased by 44% ( p<0.0001 compared with placebo) and that of deoxypyridinoline by 18% ( p<0.0001) in the clodronate 800 mg group. In the extension study urinary NTX decreased by 51% ( p<0.0001) in those who were switched to 800 mg of clodronate and increased by 67% ( p<0.0001) in those who stopped using that dose. There was no difference in the frequency of gastrointestinal complaints between clodronate- and placebo-treated patients in the primary study, but they were more common among women who received clodronate in the extension phase. Clodronate in daily doses of 400-800 mg caused a slight elevation of aminotransferase levels, usually within the reference range. In bone biopsies no defect in mineralization was found. In conclusion, clodronate in a daily dose of 800 mg prevents early postmenopausal bone loss at the sites of the skeleton in which cancellous bone predominates. It effectively reduces bone resorption and bone turnover rate. Antifracture efficacy of clodronate remains ...

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Section: Discussionmentioning

confidence: 99%

Prevention of Bone Loss by Clodronate in Early Postmenopausal Women with Vertebral Osteopenia: A Dose-Finding Study

Välimäki

Laitinen

Patronen³

et al. 2002

Osteoporosis International

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“…Recently, McCloskey et al [18] have demonstrated that oral clodronate daily is effective in preventing bone loss, and after 1 year of therapy provides an antifracture effect in patients with established osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

Bisphosphonates in the Treatment of Thalassemia-Induced Osteoporosis

et al. 2002

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The aim of our randomized, placebo-controlled study was to investigate the effects of 2 years' daily oral administration of alendronate or intramuscular administration of clodronate every 10 days, on bone remodeling parameters and bone mineral density (BMD), safety and tolerability in a group of osteoporotic thalassemic patients. Twenty-five young patients (mean age 26.6 +/- 7.1 years) with beta-thalassemia major were randomly divided to receive placebo or 100 mg of clodronate intramuscularly every 10 days or 10 mg of alendronate per os daily. All patients took 500 mg of elemental calcium and 400 IU cholecalciferol in the evening at meal time. After 2 years, pyridinium crosslinks, which are bone resorption markers, did not differ significantly from baseline values in the placebo group, whereas they had decreased significantly in the clodronate and alendronate groups. Osteocalcin, a bone formation marker, did not change significantly in the placebo group, whereas it decreased slightly, but not significantly, in the clodronate and alendronate groups after 12 and 24 months. At the end of the study, the lumbar spine BMD had decreased significantly in the placebo group; it did not change significantly in the clodronate group; in the alendronate group it had increased but not significantly, whereas the increase was significant with respect to the placebo group. Femoral neck BMD decreased significantly in the placebo group; it did not change significantly in the clodronate group, but increased significantly in the alendronate group. No relevant side effects were recorded during our study. In conclusion, in patients with thalassemia-induced osteoporosis, the daily administration of alendronate significantly increases BMD, the most important predictor of the risk of fracture at several sites. Clodronate treatment at our dosage is ineffective in this pathology in spite of the good compliance of patients.

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“…In order to facilitate this comparison, the same dataset and performance metrics were used. The dataset consisted of 320 DXA VFA images scanned on various Hologic (Bedford MA) scanners, obtained from: a) 44 patients from a previous study [19]; b) 80 female subjects in an epidemiological study of a UK cohort born in 1946; c) 196 females attending a local clinic for DXA BMD measurement, and for whom the referring physician had also requested VFA (as approved by the local ethics committee). Manual annotations of 405 landmark points were available for each image, covering the thoracic vertebrae from T7 to T12 and the lumbar vertebrae from L1 to L4.…”

Section: Discussionmentioning

confidence: 99%

Localisation of Vertebrae on DXA Images Using Constrained Local Models with Random Forest Regression Voting

Bromiley¹,

Cootes²,

Yao³

et al. 2015

Recent Advances in Computational Methods and Clinical Applications for Spine Imaging

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Abstract. Fractures associated with osteoporosis are a significant public health risk, and one that is likely to increase with an ageing population. However, many osteoporotic vertebral fractures present on images do not come to clinical attention or lead to preventative treatment. Furthermore, vertebral fracture assessment (VFA) typically depends on subjective judgement by a radiologist. The potential utility of computeraided VFA systems is therefore considerable. Previous work has shown that Active Appearance Models (AAMs) give accurate results when locating landmarks on vertebra in DXA images, but can give poor fits in a substantial subset of examples, particularly the more severe fractures. Here we evaluate Random Forest Regression Voting Constrained Local Models (RFRV-CLMs) for this task and show that, while they lead to slightly poorer median errors than AAMs, they are much more robust, reducing the proportion of larger failures by 66%. They are thus more suitable for use in computer-aided VFA systems.

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Effects of clodronate on vertebral fracture risk in osteoporosis: a 1-year interim analysis

Cited by 43 publications

References 27 publications

Prevention of Bone Loss by Clodronate in Early Postmenopausal Women with Vertebral Osteopenia: A Dose-Finding Study

Prevention of Bone Loss by Clodronate in Early Postmenopausal Women with Vertebral Osteopenia: A Dose-Finding Study

Bisphosphonates in the Treatment of Thalassemia-Induced Osteoporosis

Localisation of Vertebrae on DXA Images Using Constrained Local Models with Random Forest Regression Voting

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