Intermittent intramuscular clodronate therapy: a valuable option for older osteoporotic women

Lj, Dominguez; Galioto, Antonio; Ferlisi, Anna; Alessi, Maria Adele; Belvedere, Mario; Putignano, Ernesto; Costanza, Giuseppe; Bevilacqua, Maurizio; Barbagallo, Mario

doi:10.1093/ageing/afi160

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…17 The efficacy of clodronate in the management of osteoporosis in postmenopausal women has been documented in several studies carried across more than two decades, which have shown the effects of clodronate administered using different routes of administration and dose schedules, not only in increasing BMd, but also in reducing fragility-related fractures. Table i [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] summarizes the results of studies with clodronate in the treatment of post-menopausal osteoporosis.…”

Section: Evidence Synthesismentioning

confidence: 99%

“…nevertheless, the largest increases in BMd at the lumbar spine and femoral neck were reported in the group of patients treated with clodronate 100 mg per week. 29 More recent trials have been conducted in women with postmenopausal osteoporosis to Results of efficacy A significant increase in mean BMD was observed at the lumbar spine in patients receiving clodronate (4.21% in group A and 2.98% in group B), whereas no significant changes were reported in patients receiving only calcium and vitamin D (-0.50%). The difference between groups A and B was statistically significant at both the lumbar spine (P=0.02) and the femoral neck (P=0.05).…”

Section: Clodronate In Primary Osteoporosismentioning

confidence: 99%

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Clodronate in the management of different musculoskeletal conditions

Frediani¹,

Giusti²,

Bianchi³

et al. 2018

Minerva Med

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inTrOdUcTiOn: clodronic acid is a non-nitrogen-containing bisphosphonate largely used from some decades in the prevention and treatment of postmenopausal and secondary osteoporosis. in addition to antiresorptive activity, clodronate has shown anti-inflammatory and analgesic properties, and modulatory effects on bone and cartilage metabolism. evidence acQUiSiTiOn: a literature review has been conducted to characterize the mechanism of action of clodronate and to retrieve available evidence about the use of clodronate in primary and secondary osteoporosis, and its potential role in other musculoskeletal conditions and orthopedic surgery. EVIDENCE SYNTHESIS: The efficacy and safety of the available clodronate formulations (oral, intravenous and intramuscular) in the prevention and treatment of postmenopausal and secondary osteoporosis, including corticosteroidinduced osteoporosis and bone mass loss secondary to endocrine, gastrointestinal and neoplastic diseases, have been demonstrated in a variety of clinical trials. The analgesic, anti-inflammatory, bone-and chondro-modulating properties of clodronate have allowed to expand its use in other musculoskeletal conditions to those currently approved. clodronate has proven to be beneficial in the treatment of osteoarthritis of the knee and of the hand, in the management of complex regional pain syndrome, and in the peri-and postoperative phase in subjects undergoing arthroplasty. cOncLUSiOnS: The analysis of the available literature has shown that clodronate has relevant musculoskeletal effects beyond the antiresorptive activity. Further research is needed to better position clodronate therapy in the management of these conditions and to define the optimal formulation and dose regimen in any of the tested new indications.

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Section: Evidence Synthesismentioning

confidence: 99%

Section: Clodronate In Primary Osteoporosismentioning

confidence: 99%

Clodronate in the management of different musculoskeletal conditions

Frediani¹,

Giusti²,

Bianchi³

et al. 2018

Minerva Med

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“…In particular, in a study of 250 women who were 12 months postmenopausal, Domeninguez et al compared weekly intramuscular administration of clodronate 100 mg with administration of the same dose every two weeks, and have found that both regimens achieved a statistically significant improvement in bone mineral density compared with the control group treated only with calcium and vitamin D supplementation. Nevertheless, it seemed that the largest increases in bone mineral density at the lumbar spine and femoral neck was recorded in the patient group treated with clodronate 100 mg per week 23. The improvement in bone mineral density and ability of clodronate to reduce the incidence of fractures were confirmed by Frediani et al, who conducted a study in 163 patients with arthritis and corticosteroid-induced osteoporosis 24.…”

Section: Historical Backgroundmentioning

confidence: 92%

Clinical utility of clodronate in the prevention and management of osteoporosis in patients intolerant of oral bisphosphonates

Muratore¹,

Quarta²,

Quarta³

2011

DDDT

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Bisphosphonates have a long history in the treatment of osteoporosis and bone-related disease. This review focuses on the use of a specific nonaminobisphosphonate, clodronate, which appears to be much better tolerated than other bisphosphonates and free of high-risk contraindications. Specifically, this paper reviews its use in the prevention of osteoporosis in postmenopausal women, taking into account its tolerability profile and recent safety issues arising regarding the use of bisphosphonates.

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“…Dominguez et al tested molecule efficacy in increasing BMD at a dose of 100 mg/week vs once every two weeks. Better results were obtained with the first posology both at lumbar and femoral level, although with both doses significantly higher increases of BMD were obtained, compared to the control group, treated only with calcium and vitamin D (38). In 2003 our working group published a study on the use of 100 mg clodronate one a week, intramuscularly administered on patients suffering from arthritis, about to start a cortico steroid treatment.…”

Section: Clodronate As Antiresorptive In Osteoporosismentioning

confidence: 99%

“…As for other bisphosphonates, even for clodronate, for this indication, is planned an oral administration under daily regimen, even though there is still a lack of bridging studies that aim to prove the dose equivalence between oral and parenteral (intramuscular and intravenous) administration. There are studies that show the efficacy of intramuscular administration in postmenopausal bone loss prevention (30,31) and reduction of fracture risk in glucocorticoid osteoporosis (32).…”

Section: Introductionmentioning

confidence: 99%

Clodronate: new directions of use

Frediani

Bertoldi

2015

ccmbm

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SummaryClodronate is the father of bisphosphonates. For over three decades it has been subject of study in biological and clinical areas, proving to be an extremely interesting molecule from different points of view. It has been the first drug for osteoporosis that can be administered pulsatorily (once every 15 days or once a week). This, along with good tolerability, has been the first cause of its success, when there were no solid data in literature about its antifracture efficacy. There are three published studies that prove its antifracture effect: two by McCloskey published in 2004 and 2007 on BMR, and our study about fracture prevention in corticosteroids OP. In these studies a dose of 800 mg/day orally administered or 100 mg/week I.M. was used, and they are basically the same if you consider that clodronate absorption, orally administered, is on average 1.9%. However, a series of works where higher doses were used (1600 mg orally administered) with greater effectiveness on bone mass, especially in higher risk populations, lead us to consider the use of 200 mg i.m. formulation. First of all, we proved densitometric equivalence of 200 mg i.m./14 days and 100 mg i.m./week in a first study; then, in a second study, we proved a greater densitometric efficacy of 200 mg/week compared to 100 mg/week, clearer at femoral level, where the drug had not proven to prevent femoral fracture because of inadequate bone mass increase at that level. Moreover, as for ibandronate case, monthly dose was doubled compared to pivotal trial, in order to maximize the effects on femoral bone mass and therefore prevent femoral fractures. Consequently, on the basis of the risk envelope, whether it is identified according to BMD and the presence of one risk factor at least or more correctly identified through risk chart (FRAX or DeFRA), you can put forward a differential use of 100 mg i.m. and 200 mg i.m., weekly, "off-label" or every 14 days, adjusting doses in relation to fracture risk and painful symptoms gravity, as well as improving its ease of use and therefore assist compliance. Common experience and clinical and biological works have proved that clodronate has an analgesic effect that can be increased by doubling the doses. The analgesic effect is present not only with patients with fractures, but also with patients suffering from osteoarthritis or arthritis. Therefore, the drug would fit well in the therapeutic program of rheumatic patient, also because of its symptomatic effects. Clodronate at small doses (2 mg) could also have protective effects on cartilage (introduction of intra-articular formulation is expected) and at 10-100 fold higher doses it has certainly anti-inflammatory effects and more specifically antimacrophage and anticytokine effects (IL-1, IL-6, TNFalpha, PGE). These effects are amplified by putting clodronate in monolayer liposomes. This drug, therefore, has to be considered as adjuvant in arthritis therapy, whose origin can be linked to a strong osteoclastic activation caused by an increase of cytokines and...

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Intermittent intramuscular clodronate therapy: a valuable option for older osteoporotic women

Cited by 6 publications

References 27 publications

Clodronate in the management of different musculoskeletal conditions

Clodronate in the management of different musculoskeletal conditions

Clinical utility of clodronate in the prevention and management of osteoporosis in patients intolerant of oral bisphosphonates

Clodronate: new directions of use

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