Combined effects of zoledronate and mechanical stimulation on bone adaptation in an axially loaded mouse tibia

Stadelmann, Vincent A.; Bonnet, Nicolas; Pioletti, Dominique P.

doi:10.1016/j.clinbiomech.2010.08.014

Cited by 28 publications

(20 citation statements)

References 24 publications

(32 reference statements)

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“…Overall, in the current study, both protocols increased the ultimate displacement and energy-to-fracture of tibiae loaded for 6 weeks. Despite accrual of cortical bone, WashU loading did not significantly increase tibial strength as would be expected [26], although non-significant trends were noted. Our study may have been underpowered to detect these modest changes (mean 8% for ultimate force of WashU groups).…”

Section: Discussionmentioning

confidence: 75%

Adaptation of Tibial Structure and Strength to Axial Compression Depends on Loading History in Both C57BL/6 and BALB/c Mice

et al. 2013

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Tibial compression can increase murine bone mass. However, loading protocols and mouse strains differ between studies which may contribute to conflicting results. We hypothesized that bone accrual is influenced more by loading history than by mouse strain or animal handling. The right tibiae of 4-month C57BL/6 and BALB/c mice were subjected to axial compression (10 N, 3 days/week, 6 weeks). Left tibiae served as contralateral controls to calculate relative changes [(Loaded-Control)/Control]. The WashU protocol applied 60 cycles/day, at 2 Hz, with 10 s rest-insertion between cycles; the Cornell/HSS protocol applied 1200 cycles/day, at 6.7 Hz, with 0.1 s rest-insertion. Because sham loading, sedation and transportation did not affect tibial morphology, unhandled mice served as age-matched controls (AC). Both loading protocols were anabolic for cortical bone, but Cornell/HSS loading elicited a more rapid response that was greater than WashU loading by 13%. By 6 weeks, cortical bone volume of each loading group was greater than of AC (avg. +16%) and not different from each other. Ultimate displacement and energy-to-fracture were greater in tibiae loaded by either protocol and ultimate force was greater with Cornell/HSS loading. At 6 weeks, independent of mouse strain, the WashU protocol produced minimal trabecular bone and the trabecular bone volume fraction of Cornell/HSS tibiae was greater than of AC by 65% and of WashU by 44%. We concluded that tibial adaptation to loading was more influenced by waveform than mouse strain or animal handling and therefore may have targeted similar osteogenic mechanisms in C57BL/6 and BALB/c mice.

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Section: Discussionmentioning

confidence: 75%

Adaptation of Tibial Structure and Strength to Axial Compression Depends on Loading History in Both C57BL/6 and BALB/c Mice

et al. 2013

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“…After finding of this dose, they implanted 0.3 mg of ZOL in rat femurs for 3, 6, and 9 weeks. The peri-implant bone density was found to be 4% greater with the calculated dose compared to the dose empirically by the model described as best (Stadelmann et al, 2011). Stadelmann and associates also assessed the combined effects of ZOL and mechanical loading on bone adaptation using an in vivo axial compression model of the mouse tibia and subcutaneous injection (80 ml) of ZOL.…”

Section: Implantsmentioning

confidence: 99%

“…Structures of bone were studied using mCT (microcomputed tomography) before and after the stimulation and the mechanical properties of the tibias were evaluated with three point-bending tests after sacrifice. They found that the axial loading induced a localized increase of cortical thickness and bone area (Stadelmann et al, 2011). Bobyn and associates assessed the effectiveness of ZOL in adult mongrel dogs using HA-coated porous tantalum implant conjugated with ZOL.…”

Section: Implantsmentioning

confidence: 99%

Bisphosphonates: therapeutics potential and recent advances in drug delivery

et al. 2014

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Context: Bisphosphonates (BPs) are widely used for prevention and treatment of osteoporosis. BPs are known as gold standard for osteoporosis (OP) treatment due to their positive results in clinical studies. But some serious side effects are associated with BPs like gastrointestinal adverse effect i.e. esophagitis and ulcer of esophagus. Oral bioavailability (BA) of BPs ranges from 0.6 to 1% due to poor absorption through gastrointestinal tract (GIT). Objective: The main objective of this review is to explore the role of novel drug delivery systems (DDSs) for the delivering of BPs and minimizing the drawbacks associated with them. Methods: The current review is focusing on classification, mechanism of action, and limitations of BPs, and is also dwelling on the use of novel DDSs like nanoparticles, liposomes, topical, transdermal systems, implants, bisphosphonate osteotropic DDS (BP-ODDS), microspheres, and calcium phosphate cements (CPCs) for BPs. This review also gives a critically reviewed compilation of the various in vitro and in vivo studies conducted till date. Conclusion: On the basis of the exhaustive literature, it has been found that the novel DDS minimizes the side effects associated with BPs and enhances the BA. The advance drug delivery has a greater impact on reducing the undesirable effects and increasing the BA of BPs.

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“…Although in an axially loaded mouse tibia model the interaction between the zoledronate and loading seemed to suggest a negative interaction especially at high levels of applied strain [71], supplementing mechanical stimuli with low-dose cyclosporine A seemed to be beneficial to the senescent skeleton and may augment bone mass [72]. It therefore seems reasonable to suggest that more studies are needed to better understand the relationship between these pathways.…”

Section: Effects Of Nutritional and Lifestyle Factors On The Aging Bonementioning

confidence: 96%

“…Along the same lines, interactions of pharmaceutical agents such as zoledronate, a bisphosphonate [71], and cyclosporine A [72] have been studied in mice, which have been mechanically loaded to test the potential interactions between the two regimens. Although in an axially loaded mouse tibia model the interaction between the zoledronate and loading seemed to suggest a negative interaction especially at high levels of applied strain [71], supplementing mechanical stimuli with low-dose cyclosporine A seemed to be beneficial to the senescent skeleton and may augment bone mass [72].…”

Section: Effects Of Nutritional and Lifestyle Factors On The Aging Bonementioning

confidence: 99%

Rodent Models of Aging Bone: An Update

Syed

Melim

2011

Curr Osteoporos Rep

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With an increase in the average life span especially in the Western hemisphere, there is renewed interest in treating maladies of old age including osteoporosis. Age-related bone loss and resultant osteoporosis substantially increase risk of fractures and morbidity in the geriatric population leading to both a decline in the quality of life for the elderly as well as a substantial burden on the health care system. Herein, we review recent research in murine and rodent models looking at how both extrinsic and intrinsic factors such as hormones, biochemicals, neuromodulators, inflammatory cytokines, oxidative stress, nutrition, and exercise influence the skeleton with age. Recent studies on the relationship between bone and fat in the marrow, and the fate of the marrow mesenchymal stromal cell population, which can give rise to either bone-forming osteoblasts or fat-forming adipocytic cells as a function of age, have also been highlighted. An appreciable range of studies using aging murine as well as cellular models are discussed, as these studies have broadened our understanding of the pathways and players in the aging bone. Impactful information regarding aging and the bone may then allow the application of better pharmacologic as well as nonpharmacologic regimens to alleviate bone loss due to aging.

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Combined effects of zoledronate and mechanical stimulation on bone adaptation in an axially loaded mouse tibia

Cited by 28 publications

References 24 publications

Adaptation of Tibial Structure and Strength to Axial Compression Depends on Loading History in Both C57BL/6 and BALB/c Mice

Adaptation of Tibial Structure and Strength to Axial Compression Depends on Loading History in Both C57BL/6 and BALB/c Mice

Bisphosphonates: therapeutics potential and recent advances in drug delivery

Rodent Models of Aging Bone: An Update

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