Zoledronic acid improves femoral head sphericity in a rat model of perthes disease

Little, David; McDonald, Michelle M.; Sharpe, IT; Peat, Rachel A.; Williams, Paul; McEvoy, Tony

doi:10.1016/j.orthres.2004.11.015

Cited by 67 publications

(45 citation statements)

References 32 publications

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“…143 Potential applications of bisphosphonates in orthopedics include protection against loosening of prostheses, 144 better integration of biomaterials and implants, improved healing in distraction osteogenesis, 145 and conserving bone architecture after osteonecrosis 146,147 and in Perthes disease. 148 There are potentially important differences between clinically useful bisphosphonates regarding their potency and duration of action. Efficacy is closely related to affinity for bone mineral and ability to inhibit FPP synthase.…”

Section: Some Current Issues With Bisphosphonates: Bone Architecturementioning

confidence: 99%

Bisphosphonates: Mode of Action and Pharmacology

2007

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The profound effects of the bisphosphonates on calcium metabolism were discovered over 30 years ago, and they are now well established as the major drugs used for the treatment of bone diseases associated with excessive resorption. Their principal uses are for Paget disease of bone, myeloma, bone metastases, and osteoporosis in adults, but there has been increasing and successful application in pediatric bone diseases, notably osteogenesis imperfecta. Bisphosphonates are structural analogues of inorganic pyrophosphate but are resistant to enzymatic and chemical breakdown. Bisphosphonates inhibit bone resorption by selective adsorption to mineral surfaces and subsequent internalization by bone-resorbing osteoclasts where they interfere with various biochemical processes. The simpler, non-nitrogen-containing bisphosphonates (eg, clodronate and etidronate) can be metabolically incorporated into nonhydrolysable analogues of adenosine triphosphate (ATP) that may inhibit ATP-dependent intracellular enzymes. In contrast, the more potent, nitrogen-containing bisphosphonates (eg, pamidronate, alendronate, risedronate, ibandronate, and zoledronate) inhibit a key enzyme, farnesyl pyrophosphate synthase, in the mevalonate pathway, thereby preventing the biosynthesis of isoprenoid compounds that are essential for the posttranslational modification of small guanosine triphosphate (GTP)-binding proteins (which are also GTPases) such as Rab, Rho, and Rac. The inhibition of protein prenylation and the disruption of the function of these key regulatory proteins explains the loss of osteoclast activity. The recently elucidated crystal structure of farnesyl diphosphate reveals how bisphosphonates bind to and inhibit at the active site via their critical nitrogen atoms. Although bisphosphonates are now established as an important class of drugs for the treatment of many bone diseases, there is new knowledge about how they work and the subtle but potentially important differences that exist between individual bisphosphonates. Understanding these may help to explain differences in potency, onset and duration of action, and clinical effectiveness.www.pediatrics.org/cgi

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Section: Some Current Issues With Bisphosphonates: Bone Architecturementioning

confidence: 99%

Bisphosphonates: Mode of Action and Pharmacology

2007

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“…The study, however, lacked a control group. In the studies examining the patients with leukemia or malignancy, a long-term radiographic benefit from BPs was not observed in three of six patients needing Volume The experimental studies looking at BP therapy of femoral head deformity consisted of both small-animal [28,29,34,35] and large-animal [3,12,17,45] models of femoral head ischemia (Table 3). In immature rats, the effects of zoledronic acid (the most potent aminobisphosphonate clinically available) were investigated in a surgically induced osteonecrosis model and in spontaneously hypertensive rats that develop a LCPD-like osteonecrosis.…”

Section: Resultsmentioning

confidence: 99%

“…This left eight articles for full review by three reviewers (HKWK, DGL, MLY) [3,12,17,28,29,34,35,45] (Fig. 3).…”

Section: Steroidsmentioning

confidence: 99%

Evidence for Using Bisphosphonate to Treat Legg-Calvé-Perthes Disease

Young

Little

Kim

2012

Clinical Orthopaedics &Amp; Related Research

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Background The rationale for using bisphosphonate (BP) therapy for Legg-Calvé-Perthes disease (LCPD) is the potential to prevent substantial femoral head deformity during the fragmentation phase by inhibiting osteoclastic bone resorption. However, it is unclear whether BP therapy decreases femoral head deformity. Questions/purposes In this systematic review, we answered the following questions: (1) Does bisphosphonate (BP) therapy decrease femoral head deformity and improve pain and function in LCPD or other juvenile osteonecrotic conditions? And (2) does BP therapy decrease femoral head deformity in experimental studies of juvenile femoral head osteonecrosis? Methods We searched the literature from 1966 to 2011 for clinical and experimental studies on BP therapy for juvenile femoral head osteonecrosis. Studies specifically addressing clinical and/or radiographic/histologic outcomes pertaining to pain and function and femoral head morphology were analyzed.

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“…Autores descreveram os resultados de trabalhos com uso de bisfosfonatos em modelos animais na afecção de Legg-Calvé-Perthes visando, pela ação antiosteoclástica, atenuar a fase de reabsorção (32) .…”

Section: Discussionunclassified