New model for simulation of fracture repair in full-grown beagle dogs: Model characterization and results from a long-term study with ibandronate

Bauss, Frieder; Schenk, Robert K.; Hört, Stefan; Müller-Beckmann, B.; Sponer, G.

doi:10.1016/j.vascn.2003.11.003

Cited by 44 publications

(37 citation statements)

References 31 publications

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“…140 Studies of repair processes after creating drill-hole defects in dogs also showed no impairment with ibandronate. 141 Several other recent studies raised the intriguing possibility that bisphosphonates may enhance fracture repair and related processes. 142 In studies of the osseointegration of metal implants in ovariectomized rats, treatment with ibandronate resulted in improved osseointegration rather than impairment of the healing process.…”

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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“…Animal studies have reported controversial results, with some articles reporting delays in fracture healing [11][12][13], no effect [14,15], or even enhanced fracture healing [16][17][18][19][20][21]. Some case reports suggest that a potential complication of long-term BP therapy may be a delay in fracture healing in humans [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Timing of the initiation of bisphosphonates after surgery for fracture healing: a systematic review and meta-analysis of randomized controlled trials

Cai

Zhang

2014

Osteoporos Int

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“…11 Because they suppress bone remodeling, it has been hypothesized that bisphosphonates can interfere with fracture healing. 12 Animal studies have provided controversial evidence, reporting delays in fracture healing, 13,14 no effect, 15,16 or even enhanced fracture healing. [17][18][19][20] In general, animal studies have shown that, whereas the early stages are relatively unaffected, remodeling of the bony callus may be delayed by bisphosphonate treatment.…”

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confidence: 99%