Intracortical remodeling in adult rat long bones after fatigue loading

Bentolila, V.; Boyce, T. M.; Fyhrie, David P.; Drumb, R.; Skerry, Timothy M.; Schaffler, Mitchell B.

doi:10.1016/s8756-3282(98)00104-5

Cited by 406 publications

(437 citation statements)

References 33 publications

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“…The cortical bone of the rat lacked the primary and secondary osteons that were present in both the human and the sheep. These findings are supported by the observations of other investigators (Frost and Jee, 1992;Newman et al, 1995;Bentolila et al, 1998), who found that the rat normally lacks Haversian remodeling, except in extreme mechanical loading situations and in the occasional older rat. This is the first investigation to compare the percent ash of calcified fibrocartilage from tendon insertions between different species.…”

Section: Discussionsupporting

confidence: 88%

Experimental confirmation of the sheep model for studying the role of calcified fibrocartilage in hip fractures and tendon attachments

Shea¹,

Hallows²,

Bloebaum³

2002

Anat. Rec.

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Research has shown that there is a dramatic increase in the fractional area of calcified fibrocartilage from tendon and capsular insertions on the human femoral neck Shea et al., 2001b). Additional information regarding the properties of the proximal femur's cortical shell, gained from the use of an animal model, may result in a better understanding of elderly hip fracture since the cortical shell is a significant contributor to the strength of the proximal femur. The objective of the present study was to determine if the greater trochanter's tendon insertions of the human, rat, and sheep differ in terms of morphology and mineralization. The tendons of the greater trochanter of the human, rat, and sheep were observed to insert via a fibrocartilage insertion. The mineral content of the human and sheep calcified fibrocartilage was significantly higher than that of the rat calcified fibrocartilage (P Ͻ 0.01). Additionally, the mineral content of the rat cortical bone was significantly higher than that of the human cortical bone (P Ͻ 0.01). The mineral content of the calcified fibrocartilage and bone of the human and sheep were not statistically different from each other. There were also more similarities between the bone structure and lacunae density of the human and sheep than between the human and the rat. This suggests that the tendon insertions of the sheep are a better model than the tendon insertions of the rat for the investigation of calcified fibrocartilage in elderly hip fractures.

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Section: Discussionsupporting

confidence: 88%

Experimental confirmation of the sheep model for studying the role of calcified fibrocartilage in hip fractures and tendon attachments

Shea¹,

Hallows²,

Bloebaum³

2002

Anat. Rec.

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“…In this study we chose for random resorption, to ensure that any adaptation to mechanical load resulted from osteocyte-osteoblast crosstalk, be it via the stimulatory or the inhibitory pathway. However, it is believed that osteoclasts target dead osteocytes for resorption (Bentolila et al 1998;Verborgt et al 2000). If the stimulatory model were combined with such targeted resorption, loss of osteocytes would result in an even greater loss of trabeculae than was seen here.…”

Section: Discussionmentioning

confidence: 70%

A sclerostin-based theory for strain-induced bone formation

Oers

Rietbergen

Ito

et al. 2010

Biomech Model Mechanobiol

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Bone formation responds to mechanical loading, which is believed to be mediated by osteocytes. Previous theories assumed that loading stimulates osteocytes to secrete signals that stimulate bone formation. In computer simulations this 'stimulatory' theory successfully produced loadaligned trabecular structures. In recent years, however, it was discovered that osteocytes inhibit bone formation via the protein sclerostin. To reconcile this with strain-induced bone formation, one must assume that sclerostin secretion decreases with mechanical loading. This leads to a new 'inhibitory' theory in which loading inhibits osteocytes from inhibiting bone formation. Here we used computer simulations to show that a sclerostin-based model is able to produce a load-aligned trabecular architecture. An important difference appeared when we compared the response of the stimulatory and inhibitory models to loss of osteocytes, and found that the inhibitory pathway prevents the loss of trabeculae that is seen with the stimulatory model. Further, we demonstrated with combined stimulatory/inhibitory models that the two pathways can work side-by-side to achieve a load-adapted bone architecture.

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“…(17,45) There is some concern that an inhibition of bone turnover may result in an increase in bone fragility through the accumulation of microfracture damage. (48)(49)(50) In healthy bone, the accumulation of microfractures over time is controlled by targeted bone remodeling. (48,49) Abrogation of bone remodeling therefore may increase the level of skeletal microdamage and lead to bone with decreased mechanical strength.…”

Section: Discussionmentioning

confidence: 99%

“…(48)(49)(50) In healthy bone, the accumulation of microfractures over time is controlled by targeted bone remodeling. (48,49) Abrogation of bone remodeling therefore may increase the level of skeletal microdamage and lead to bone with decreased mechanical strength. (50) In support of this, several studies have suggested that long-term inhibition of bone turnover by bisphosphonates may result in increased microfracture accumulation and, in some cases, decreased bone strength.…”

Section: Discussionmentioning

confidence: 99%

The tyrosine kinase inhibitor dasatinib dysregulates bone remodeling through inhibition of osteoclasts in vivo

Vandyke

Dewar

Diamond

et al. 2010

Journal of Bone and Mineral Research

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Dasatinib is a potent tyrosine kinase inhibitor that is used to treat chronic myeloid leukemia in patients resistant or intolerant to imatinib mesylate. While designed to inhibit Abl and Src kinases, dasatinib shows multitarget effects, including inhibition of the macrophage colony-stimulating factor (M-CSF) receptor c-fms. We have shown previously that dasatinib abrogates osteoclast formation and activity in vitro owing, in part, to its specificity for c-fms. In this study we examined whether dasatinib could significantly alter bone volume in a model of physiologic bone turnover. Sprague-Dawley rats were administered dasatinib (5 mg/kg/day) or vehicle by gavage or zoledronic acid (ZOL; 100 mg/kg/6 weeks) subcutaneously. Following 4, 8, and 12 weeks of treatment, serum biochemical, bone morphometric, and histologic analyses were performed. Whole-body bone mineral density and tibial cortical thickness where unchanged in the dasatinib-or ZOL-treated animals relative to controls. However, micro-computed tomographic (mCT) analysis of cancellous bone at the proximal tibias showed that trabecular volume (BV/TV) and thickness (Tb.Th) were increased in dasatinib-treated animals at levels comparable with those of the ZOL-treated group. These changes were associated with a decrease in osteoclast numbers (N.Oc/B.Pm) and surface (Oc.S/BS) and decreased serum levels of the osteoclast marker c-terminal collagen crosslinks (CTX-1). Mineral apposition rate (MAR), bone-formation rate (BFR), and levels of the serum osteoblast markers osteocalcin and N-terminal propeptide of type I procollagen (P1NP) were not altered significantly in the dasatinib-treated animals relative to controls. These studies show that dasatinib increases trabecular bone volume at least in part by inhibiting osteoclast activity, suggesting that dasatinib therapy may result in dysregulated bone remodeling. ß

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Intracortical remodeling in adult rat long bones after fatigue loading

Cited by 406 publications

References 33 publications

Experimental confirmation of the sheep model for studying the role of calcified fibrocartilage in hip fractures and tendon attachments

Experimental confirmation of the sheep model for studying the role of calcified fibrocartilage in hip fractures and tendon attachments

A sclerostin-based theory for strain-induced bone formation

The tyrosine kinase inhibitor dasatinib dysregulates bone remodeling through inhibition of osteoclasts in vivo

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