Intravenous Zoledronic Acid in Postmenopausal Women with Low Bone Mineral Density

Reid, Ian R.; Brown, Jacques P.; Burckhardt, P.; Horowitz, Zebulun D.; Richardson, Peter; Trechsel, U.; Widmer, A.; Devogelaer, J.-P.; Kaufman, Jean; Jaeger, Philippe; Body, Jean Jacques; Brandi, Maria Luisa; Broell, Johann; Micco, Raffaele Di; Genazzani, Andrea Riccardo; Felsenberg, Dieter; Happ, J.; Hooper, Michael J.; Ittner, Jochen; Leb, G.; Mallmin, Hans; Murray, Timothy M.; Ortolani, S.; Rubinacci, Alessandro; Sääf, Maria; Samsioe, Göran; Verbruggen, Leon; Meunier, Pierre J.

doi:10.1056/nejmoa011807

Cited by 772 publications

(255 citation statements)

References 24 publications

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“…Another intravenous bisphosphonate, zoledronic acid, has recently been indicated for the treatment of adult osteoporosis [16,17]; there is only little experience of its use in pediatric patients [18,19,20,21,22]. The major advantages of zoledronic acid are its superior potency compared to other bisphosphonates and long-lasting efficacy in suppressing bone turnover, allowing less frequent administration.…”

Section: Introductionmentioning

confidence: 99%

Zoledronic Acid Treatment in Children with Osteogenesis Imperfecta

et al. 2011

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Background: Intravenous disodium pamidronate has become an established treatment in osteogenesis imperfecta (OI). Another bisphosphonate, zoledronic acid, has been indicated for the treatment of adult osteoporosis. We studied its efficacy and safety in children with mild OI. Methods: Patients were treated for 1.0–3.2 years with 0.05 mg/kg zoledronic acid intravenously every 6 months as part of their clinical care. They were carefully followed for clinical and biochemical parameters, side effects, bone mineral densities (BMD) and compression fractures. Results: The study included 17 patients (age 1.5–16.8 years) with type I OI. They had sustained altogether 73 fractures; 9 had compression fractures. During the treatment, 6 patients suffered in total 10 new long-bone fractures. The median lumbar spine areal BMD z-score increased from –2.0 to –0.7 during 2 years of treatment. The infusions were associated with a transient decrease in serum calcium and phosphate and a significant increase in serum PTH. Two patients developed symptomatic hypocalcemia. Bone turnover markers decreased during the treatment. Conclusions: Intravenous zoledronic acid is an effective mode of treatment in children with OI. The treatment response is comparable to pamidronate but the infusion protocol is more convenient. Further studies are needed to establish optimal dosing and long-term safety.

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Section: Introductionmentioning

confidence: 99%

Zoledronic Acid Treatment in Children with Osteogenesis Imperfecta

et al. 2011

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“…Bone biochemical markers are increasingly used for early assessment of the response to therapy for osteoporosis. However, these marker tests cannot replace BMD testing to monitor long-term exploratory effects, because in humans, BMD changes several percent per year, whereas the bone turnover markers rapidly change several dozen percent per week, after the initiation of antiresorptive treatment [38,39]. For that reason, we evaluated BMD loss at the lumbar vertebrae and the femurs in the three studies.…”

Section: Discussionmentioning

confidence: 99%

Effect of SI-591, a new class of cathepsin K inhibitor with peptidomimetic structure, on bone metabolism in vitro and in vivo

Fujii

Ishikawa

Kubo

et al. 2015

Bone

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SI-591[N-[1-[[[(1S)-3-[[(3S)-hexahydro-2-oxo-1H-azepin-3-yl]amino]-1-(1-methylethyl)-2,3-dioxopropyl]amino]carbonyl]cyclohexyl]-2-furancarboxamide] is an orally bioavailable compound that was synthesized as one of several unique peptidomimetic compounds without a basic group. This compound was found to have the ability to inhibit cathepsin K, a lysosomal cysteine protease. Cathepsin K is known to be expressed in osteoclasts and involved in bone loss processes. In this study, SI-591 was shown to inhibit the activity of various purified cathepsin molecules at nanomolar concentrations but had high selectivity for cathepsin K over other subtypes including B and L. SI-591 also decreased the level of CTX-I, a bone resorption marker, which was released from osteoclasts in vitro in a dose-dependent manner. The mobilization of calcium from the bones to the blood stream is known to increase in rats fed with a low calcium diet; SI-591 inhibited this increase in serum calcium level at an oral dose of 3mg/kg. Furthermore, SI-591 significantly decreased the level of CTX-I and DPD, bone resorption markers, at oral doses of 10mg/kg or less in ovariectomized rats, while it did not affect the level of BGP, a bone formation marker. In addition, SI-591 prevented bone mineral density loss in the lumber vertebrae and femurs in ovariectomized rats. These results suggest that SI-591 inhibits bone resorption without affecting osteoblast maturation. Therefore, SI-591, a novel cathepsin K inhibitor, could be a promising agent for the treatment of postmenopausal osteoporosis.

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“…Zoledronic acid is one of the newer bisphosphonates that is being used to treat postmenopausal osteoporosis [21]. Its utility for the treatment of children and adolescents with OI is currently under investigation in an international multicenter trial.…”

Section: Intravenous Pamidronatementioning

confidence: 99%

Treatment of Osteogenesis Imperfecta: Who, Why, What?

Glorieux

2007

Horm Res Paediatr

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Introduction: Osteogenesis imperfecta (OI) is a heritable disorder characterized by bone fragility and reduced bone mass. It may present with a wide range of severity. About 85% of the cases are linked to mutations in one of the two genes encoding type I collagen. In other cases of OI, there are mutations in the expression of a cartilage-related protein or of 3-prolyl-hydroxylase.Increased bone turnover rate, due to the repair activity triggered to replace weak tissue, is the rule. Often, disuse bone loss further compounds the decrease in bone mass. These findings justify the use of bisphosphonates to reduce osteoclast-mediated bone resorption, and so tilt the remodeling balance towards an increase in bone mass. Conclusions: Cyclical intravenous pamidronate administration reduces bone pain, and increases bone mass and density. No negative effects on growth or fracture repair have been observed. There is an increase in size of vertebral bodies and thickening of cortical bone, which translates into decreased fracture incidence and improved ambulation. However, the long-term consequences of low bone turnover in children with OI are unknown at the present time. Innovative surgery and specific occupational and physiotherapy programs are integral parts of the treatment protocol. This approach will prevail until gene-based therapies become clinically applicable.

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Intravenous Zoledronic Acid in Postmenopausal Women with Low Bone Mineral Density

Cited by 772 publications

References 24 publications

Zoledronic Acid Treatment in Children with Osteogenesis Imperfecta

Zoledronic Acid Treatment in Children with Osteogenesis Imperfecta

Effect of SI-591, a new class of cathepsin K inhibitor with peptidomimetic structure, on bone metabolism in vitro and in vivo

Treatment of Osteogenesis Imperfecta: Who, Why, What?

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