Poor histological healing of a femoral fracture following 12 months of oestrogen deficiency in rats

Oliver, Rema A.; Yu, Youcheng; Yee, Gary; Low, Adrian K.; Diwan, Ashish D.; Walsh, William R.

doi:10.1007/s00198-013-2345-2

Cited by 28 publications

(26 citation statements)

References 25 publications

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“…The OVX rat has been widely used as an estrogen-deficient model for the research study of post-menopausal bone loss (8–11,13,14,18–20). In addition to bone loss and the deterioration of biomechanical properties, IVD degeneration is also observed in this model.…”

Section: Discussionmentioning

confidence: 99%

Orally administered simvastatin partially preserves lumbar vertebral bone mass but not integrity of intervertebral discs in ovariectomized rats

Tian¹,

Li²,

Yang³

et al. 2017

Experimental and Therapeutic Medicine

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The present study aimed to investigate the effect of orally administered simvastatin on lumbar vertebral bone mass and intervertebral disc (IVD) degeneration in ovariectomized (OVX) rats. A total of 30 female Sprague-Dawley (SD) rats were subjected to either bilateral ovariectomy (n=20) or sham surgery (n=10). After 12 weeks, the OVX rats were orally administered either saline vehicle (OVX + V group; n=10), or 5 mg/kg/day simvastatin (OVX + SIM group; n=10). Following 12 weeks of treatment, necropsy was conducted and bone mineral density (BMD) was determined in the L5-6 vertebrae. Furthermore, the microstructure and biomechanical properties of the L3 vertebrae were detected by micro-computed tomography and compression testing, respectively. The L5-6 vertebrae were analyzed by measurement of IVD height, observation of histological changes by van Gieson staining, and evaluation of collagen-II (col-II), aggrecan (AGG) and collagen I (col-I) expression by immunohistochemical analysis. Rats in the OVX+V group had lower BMD, bone volume/trabecular volume ratio, maximum load and elastic modulus than the sham group. Rats in the OVX + SIM group had higher BMD and biomechanical strength values than the rats in the OVX+V group. Histological analysis showed that the OVX + V and OVX + SIM groups exhibited significantly higher disc degeneration scores and significantly lower IVD height than the sham group. Immunohistochemical analysis revealed lower expression levels of col-II and AGG, but higher levels of col-I in the annulus fibrosis and endplate in OVX+V rats compared with the sham group. The OVX + SIM group exhibited levels of col-II, AGG and col-I expression comparable with those of OVX+V rats, with the exception of an upregulation of col-II expression in the annulus fibrosis. These data demonstrate that simvastatin treatment partially prevented bone loss and the deterioration of biomechanical properties of lumbar vertebrae, but not the progression of IVD degeneration in OVX rats.

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Section: Discussionmentioning

confidence: 99%

Orally administered simvastatin partially preserves lumbar vertebral bone mass but not integrity of intervertebral discs in ovariectomized rats

Tian¹,

Li²,

Yang³

et al. 2017

Experimental and Therapeutic Medicine

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“…Furthermore, studies showed differences in bone healing involving less callus formation in the metaphyseal area with more endosteally bone healing than in the diaphysis during fracture healing [2,3,4,30]. Regarding the pathophysiology of osteoporotic bone, several reports suggest deviations in healing patterns in osteoporotic bone from the normal course in diaphyseal fracture model and drill-hole defects [31][32][33][34][35][36][37][38][39]. Metaphyseal fracture healing was addressed only with a couple of models, which studied either a small sized gap [4,18,22,[40][41][42] a drill-hole defect [9,[43][44][45][46] or partial osteotomy [1].…”

Section: Animal Modelsmentioning

confidence: 99%

“…Many studies suggest differences in bone healing in osteoporotic vs. physiological bone status [32,35,36,37,39]. In a comparative study between ovariectomized (OVX) and sham-operated (SHAM) rats, provided with a 3 mm wedgeshaped fracture-defect in the metaphyseal area of the femur, histological and biomechanical differences could be constituted.…”

Section: Osteoporotic Bone Healingmentioning

confidence: 99%

Biomaterials for enhancement of bone healing in osteoporotic fractures

Thormann¹,

Ray

Sommer

et al. 2013

BioNanoMaterials

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Osteoporosis and osteoporotic fractures have a high impact on the quality of life of patients and on the financial aspects of Western health care systems. There is a tremendous need for improvement of the treatment outcome in osteoporotic fracture patients and biomaterials are of interest to stimulate fracture healing in those patients. For adequate characterization of biomaterials for the indication of osteoporotic fractures a clinically relevant animal model with a fracture defect in the metaphyseal region of a long bone in an osteoporotic animal is required. We recently developed a 3-5 mm wedge shaped osteotomy model in the distal metaphysis of the femur in osteoporotic rats. There are different biomaterials approaches to stimulate fracture healing in osteoporotic fractures and recently published results suggest that the composite implants from osteoconductive carriers combined with osteoanabolic agents, e.g., strontium-modified calcium phosphate cement, can enhance new bone formation. Further in vivo and clinical research will be necessary in the future for introduction of new and different types of biomaterials for osteoporotic fracture patients into all day clinical practice.

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“…Treatment of osteoporotic fractures, particularly of osteoporotic fractures with bone defects, remains a critical challenge. Accumulating evidence suggests that osteoporosis impairs healing of fractures . The mechanisms are complex, and are associated with weak osteogenesis and angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…Accumulating evidence suggests that osteoporosis impairs healing of fractures. [2][3][4][5][6][7][8] The mechanisms are complex, and are associated with weak osteogenesis and angiogenesis. A reduction in the differentiation of mesenchymal stem cells (MSCs) into osteoblasts contributes to the impaired bone formation observed in osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

Deferoxamine released from poly(lactic‐co‐glycolic acid) promotes healing of osteoporotic bone defect via enhanced angiogenesis and osteogenesis

Jia

Chen

Kang

et al. 2016

J Biomedical Materials Res

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The regeneration capacity of osteoporotic bones is generally lower than that of normal bones. Current methods of osteoporotic bone defect treatment are not always satisfactory. Recent studies demonstrate that activation of the hypoxia inducible factor-1α (HIF-1α) pathway, by genetic methods or hypoxia-mimicking agents, could accelerate bone regeneration. However, little is known as to whether modulating the HIF-1α pathway promotes osteoporotic defect healing. To address this problem in the present study, we first demonstrated that HIF-1α and vascular endothelial growth factor expression levels are lower in osteoporotic bones than in normal bones. Second, we loaded poly(Lactic-co-glycolic acid) (PLGA) with the hypoxia-mimetic agent deferoxamine (DFO). DFO released from PLGA had no significant effect on the proliferation of mesenchymal stem cells (MSCs); however, DFO did enhance the osteogenic differentiation of MSCs. In addition, DFO upregulated the mRNA expression levels of angiogenic factors in MSCs. Endothelial tubule formation assays demonstrate that DFO promoted angiogenesis in human umbilical vein endothelial cells. Third, untreated PLGA scaffolds (PLGA group) or DFO-containing PLGA (PLGA + DFO group) were implanted into critically sized osteoporotic femur defects in ovariectomized rats. After treatment periods of 14 or 28 days, micro-CT, histological, CD31 immunohistochemical, and dynamic bone histomorphometric analyses showed that DFO dramatically stimulated bone formation and angiogenesis in a critically sized osteoporotic femur defect model. Our in vitro and in vivo results demonstrate that DFO may promote the healing of osteoporotic bone defects due to enhanced angiogenesis and osteogenesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2515-2527, 2016.

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Poor histological healing of a femoral fracture following 12 months of oestrogen deficiency in rats

Abstract: Long-term ovariectomy has a deleterious effect on fracture healing in a rodent model.

Cited by 28 publications

References 25 publications

Orally administered simvastatin partially preserves lumbar vertebral bone mass but not integrity of intervertebral discs in ovariectomized rats

Orally administered simvastatin partially preserves lumbar vertebral bone mass but not integrity of intervertebral discs in ovariectomized rats

Biomaterials for enhancement of bone healing in osteoporotic fractures

Deferoxamine released from poly(lactic‐co‐glycolic acid) promotes healing of osteoporotic bone defect via enhanced angiogenesis and osteogenesis

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