Cyclical intravenous clodronate in postmenopausal osteoporosis: Results of a long-term Clinical trial

Filipponi, P; Cristallini, S.; Rizzello, Elisa; Policani, G.; Fedeli, L.; Gregorio, F. Di; Boldrini, S.; Troiani, Stefania; Massoni, C.

doi:10.1016/8756-3282(95)00442-4

Cited by 58 publications

(26 citation statements)

References 21 publications

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“…The same study also showed an increase in risk of vertebral fractures in women with breast cancer, but these were attributed to skeletal metastases. It is likely that the risk of vertebral fracture is underestimated because half of the women with breast cancer were receiving clodronate, which has been shown to decrease the risk of vertebral fracture both in breast cancer (Paterson et al, 1993;Kanis et al, 1996) and in osteoporosis (Filipponi et al, 1996). Clodronate also decreases bone loss in women at the time of diagnosis of breast cancer (Powles et al, 1997;Saarto et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

A high incidence of vertebral fracture in women with breast cancer

et al. 1999

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Metastases from breast cancer appear to have a predilection for the skeleton. In addition to focal skeletal disease, there is evidence that breast cancer is associated with generalized disturbances in skeletal metabolism.Increased resorption and accelerated turnover of bone have been shown in biopsies taken at sites distant from skeletal metastases (Taube et al, 1994), perhaps mediated by the systemic secretion of parathyroid hormone-related protein (PTHrP) which is expressed in breast cancer tissue (Orloff et al, 1989;Powell et al, 1991).In addition to the expression of PTHrP, both chemotherapy and a chemotherapy-induced menopause are likely to increase the risk of osteoporosis (Rivkees and Crawford, 1988;Saarto et al, 1997). Whereas tamoxifen may protect against bone loss in postmenopausal women, recent evidence suggests that bone losses may be accelerated in women with normal ovarian function Saarto et al, 1997). For these reasons, we wished to determine whether the risk of osteoporotic fractures was higher in women with non-metastatic breast cancer than in the healthy population. PATIENTS AND METHODSWe studied two populations of women with breast cancer and a control population of women randomly drawn from the female population. Eighty-two women had histologically proven breast cancer and recurrent disease diagnosed according to standard criteria (Breast Cancer Task Force, 1977;Hayward et al, 1978), but without skeletal metastases as judged by skeletal radiographs and scintigraphy. They comprised a cohort of women in whom the effects of clodronate on the incidence of skeletal metastases and associated morbidity were studied. The findings of this trial have been published elsewhere .After initial assessment, patients were randomized to receive clodronate by mouth, 1600 mg daily as four capsules, or an identical placebo supplied by Leiras Oy, Helsinki, Finland. Patients were instructed to take four capsules daily in the morning 1 h before meals and away from calcium-containing liquids. Bone scintigraphy and skeletal radiographs (hands, pelvis, skull, lateral lumbar and thoracic spine) were obtained at 6-monthly intervals.The second population of women with breast cancer comprised 352 women recruited at the time of the first diagnosis to study the effects of clodronate, 1600 mg daily by mouth, on the incidence of skeletal metastases. None of the women had radiographic or scintigraphic evidence of skeletal disease. No selection was made on the basis of histological grade or the involvement of axillary nodes. After diagnosis, 36% of women received tamoxifen, 18% chemotherapy and 43% both chemotherapy and tamoxifen. After randomization to clodronate or placebo treatment, patients were assessed at 6-monthly intervals and spinal radiographs taken yearly. The study is continuing and remains double blind, so that the data are presented irrespective of treatment allocation.A control population comprised 776 women aged 45Ð69 years randomly drawn from a catchment population in London . At initial assessment, 193 women (2...

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Section: Discussionmentioning

confidence: 99%

A high incidence of vertebral fracture in women with breast cancer

et al. 1999

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“…These include individuals near the menopause, patients who have a low BMD already from the outset of glucocorticoid therapy, or those who will continue with high doses of prednisolone over a long period of time. Although bisphosphonates are efficacious in the treatment of clinically overt osteoporosis [16,17], the BMD in most patients with GCA seems to recover after one year of glucocorticoid treatment without the use of such agents. A primary prevention using bone-sparing agents would thus probably not be necessary in the majority of GCA patients.…”

Section: Discussionmentioning

confidence: 99%

“…Bisphosphonate, a medication that inhibits bone resorption, has been reported to be effective in reversing glucocorticoid-induced bone loss [13][14][15] and also in preventing the development of osteoporosis in postmenopausal patients [16,17], as well as decreasing the incidence of vertebral fractures after the menopause. Besides clodronate, the effect of other second-generation bisphosphonates on osteoporosis -such as alendronate, pamidronate, risedronate and tiludronate -has been documented [18].…”

Section: Introductionmentioning

confidence: 99%

The ineffectiveness of cyclical oral clodronate on bone mineral density in glucocorticoid‐treated patients with giant‐cell arteritis

Nordborg

Schaufelberger

Andersson

et al. 1997

Journal of Internal Medicine

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Abstract. Nordborg E, Schaufelberger C, Andersson R, Bosaeus I, Bengtsson B-Å (Sahlgrenska University Hospital, Göteborg, Sweden). The ineffectiveness of cyclical oral clodronate on bone mineral density in glucocorticoid-treated patients with giant-cell arteritis. J Intern Med 1997; 242: 367᎐71.Objectives and design. The aim of the present study was to determine whether cyclic oral administration of clodronate, a bisphosphonate, every second month prevents rapid bone loss during the first year of glucocorticoid treatment in patients with giantcell arteritis (GCA). The trial was designed as a prospective double blind study, assessing total body mineral content (BMC) and bone mineral density (BMD) using DXA technique. Supplementation of calcium was given to both groups of patients. Setting. The outpatient clinics of the rheumatic and infectious diseases of Sahlgren University Hospital of the city of Göteborg on the west coast of Sweden. Subjects. Twenty-seven patients with confirmed GCA were consecutively included during a 15-month period.Results. An early influence on bone turnover was found with a temporary decrease in BMC after six months of glucocorticoid treatment, which was normalized after 12 months in both study groups. No significant differences between the patients given clodronate and calcium and the controls, who got supplementation with calcium alone, was observed at any assessment point. However, there was a significant and prolonged depression of the osteocalcin levels in the clodronate-treated patients. Conclusions. Oral administration of clodronate in a moderately high dose given cyclically every other month had no additive effect on BMD compared with calcium supplementation alone during the first year of glucocorticoid treatment. A larger material might have revealed some differences between the categories. In most patients with GCA, however, the BMD seems to recover after one year of glucocorticoid treatment, provided there is good control of the inflammation and patients are kept physically active. It needs to be elucidated whether there are subsets of patients who might benefit from bone sparing agents: women near menopause with a high turnover rate of bone, individuals who have low BMD from the start of glucocorticoid treatment or patients requiring high doses of glucocorticoids during a long period of time.

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“…esiste una qualche documentazione della loro efficacia nel trattamento dell'osteoporosi. [72][73][74][75][76][77][78][79][80] Clodronato e alendronato sono stati i primi bisfosfonati approvati sia per il trattamento che per la prevenzione dell'osteoporosi.…”

Section: Bisfosfonatiunclassified

“…[68,69] Diversi studi hanno evidenziato l'efficacia del clodronato, un alogeno-bisfosfonato, nel trattamento dell'osteoporosi post-menopausale. [71][72][73][74][75] Un trial clinico randomizzato e controllato verso placebo in doppio cieco della durata di 3 anni con clodronato per os alla dose giornaliera di 800 mg, ne ha dimostrata l'efficacia clinica sia nelle donne con osteoporosi postmenopausale sia in quelle con la forma secondaria. Al termine dello studio il trattamento con clodronato è stato associato ad un aumento significativo della massa ossea a livello del rachide, mentre, a differenza di quanto osservato nel gruppo placebo, la terapia mantiene inalterata la massa ossea dell'anca.…”

Section: Bisfosfonatiunclassified

Osteoporosi: la malattia e il suo costo sanitario

Zara

Pepa

Pradelli

et al. 2002

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Osteoporosis is a disorder of bone re-modeling, characterized by loss of its micro-architecture and decreased bone density, which lead to fragility and high risk of fracture following moderate traumata. Osteoporosisrelated pathological fractures occur more frequently in post-menopausal women, and the WHO estimates that the risk of osteoporotic fractures in women is approximately 40% during lifetime. The prevention of these osteoporotic fractures is considered one of the primary objectives for the control of the economical health burden of modern societies. The first part of this paper briefly outlines the physio-pathological basis, the epidemiology, the diagnosis and the available treatment options for osteoporosis, with particular regard to those therapies that are able to reduce the incidence of pathological fractures, that represent the main cost factor of the disease. In the second part, we reviewed the economical evaluations published on the cost of illness and of the costefficacy of the treatments. The studies that have analyzed the cost of osteoporosis, although incompletely, highlight that the greatest expenditures are related to hospitalization and rehabilitation after hip fracture, while the cost for the pharmacological treatment is relatively low. The cost-efficacy and cost-utility analyses conducted on pharmacological treatment are quite heterogeneous, and therefore hardly comparable, beside being conducted in countries with different health systems; the obtained data are nor directly transferable to the Italian setting. However, it emerges that diphosphonates, estrogens and SERMs (selective estrogen receptor modulators) are among the drugs with more favorable cost/effectiveness ratio, but there is still an uncertainty in the detection of the appropriate patient groups, which is crucial for the clinical, economical and ethical optimization of prevention interventions. Farmeconomia e percorsi terapeutici 2002; 3 (4): 185-208 INTRODUZIONEL'osteoporosi è un disturbo del rimodellamento del tessuto osseo che comporta deterioramento della sua microarchitettura, perdita di densità ossea, aumento della fragilità scheletrica e quindi notevole incremento del rischio di fratture in seguito a traumi di minima intensità. [1] Le fratture da osteoporosi si verificano con maggior frequenza nelle donne anziane a causa del naturale declino della densità ossea dopo la menopausa. L'Organizzazione Mondiale della Sanità (OMS) stima che il 15% delle donne europee ed americane ed il 35% delle donne con età superiore ai 65 anni presentino segni clinici evidenti di osteoporosi. Inoltre, il 50% delle donne mostra i segni più o meno evidenti di una diminuzione nella densità ossea all'articolazione dell'anca. Attualmente il rischio di incorrere in una frattura osteoporotica nel corso della vita è stimato nel 40% per le donne e nel 13% per gli uomini. [1,2] L'osteoporosi rappresenta, dunque, un elevato carico sanitario ed economico soprattutto per le società sviluppate ad alto tasso d'invecchiamento. Nei prossimi decenni ...

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Cyclical intravenous clodronate in postmenopausal osteoporosis: Results of a long-term Clinical trial

Cited by 58 publications

References 21 publications

A high incidence of vertebral fracture in women with breast cancer

A high incidence of vertebral fracture in women with breast cancer

The ineffectiveness of cyclical oral clodronate on bone mineral density in glucocorticoid‐treated patients with giant‐cell arteritis

Osteoporosi: la malattia e il suo costo sanitario

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