Osteoclasts prefer aged bone

Henriksen, Kim; Leeming, Diana Julie; Byrjalsen, I.; Nielsen, Rasmus Hjorth; Sørensen, Mette G; Dziegiel, Morten Hanefeld; Martın, Thomas; Christiansen, Claus; Qvist, Per; Karsdal, Morten A.

doi:10.1007/s00198-006-0298-4

Cited by 67 publications

(45 citation statements)

References 48 publications

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“…Bone matrix quality thus comprises the organization and extent of mineralization, structural changes in type I collagen molecules, and microscopic tissue damage occurring in this tissue. Central events regulating these properties of bone matrix quality are controlled by the rate of bone remodeling [21,[30][31][32][33]. The mineralization of the bone matrix is dependent on the age of the bones, with older bones being more mineralized because of alterations in bone-remodeling rates [34].…”

Section: What Is Bone Matrix Quality?mentioning

confidence: 99%

“…The rate at which these transformations occur and eventually accumulate in bone tissue is controlled by the level of bone remodeling [31,43]. This continuous remodeling of bone involves the function of osteoclasts, which act to achieve a coordinated and balanced resorption of aged bone, and of osteoblasts, responsible for sufficient formation of new bone, occurring in a localized, coordinated, and sequential manner referred to as coupling [44].…”

Section: What Is Bone Matrix Quality?mentioning

confidence: 99%

“…It has been shown that the mean age of bone assessed by αα/ββ CTX is lower in bone that is highly remodeled (trabecular bone) versus higher in less remodeled bone (cortical bone) [53]. Ex vivo experiments using bovine bone tissue or human vertebral bodies have also shown an association between the extent of type I collagen To maintain optimal quality of bone tissue, continuous remodeling of the bone matrix is essential, and the rate of remodeling controls the age of the bone matrix [17,21,22,[30][31][32][33]43]. The important contribution of bone remodeling as an independent determinant of fracture risk in both untreated and antiresorptive-treated subjects has been demonstrated using systemic biochemical markers [7,8,54,55].…”

Section: What Is Bone Matrix Quality?mentioning

confidence: 99%

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Is bone quality associated with collagen age?

et al. 2009

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The World Health Organization defines osteoporosis as a systemic disease characterized by decreased bone tissue mass and microarchitectural deterioration, resulting in increased fracture risk. Since this statement, a significant amount of data has been generated showing that these two factors do not cover all risks for fracture. Other independent clinical factors, such as age, as well as aspects related to qualitative changes in bone tissue, are believed to play an important role. The term "bone quality" encompasses a variety of parameters, including the extent of mineralization, the number and distribution of microfractures, the extent of osteocyte apoptosis, and changes in collagen properties. The major mechanism controlling these qualitative factors is bone remodeling, which is tightly regulated by the osteoclast/osteoblast activity. We focus on the relationship between bone remodeling and changes in collagen properties, especially the extent of one posttranslational modification. In vivo, measurements of the ratio between native and isomerized C-telopeptides of type I collagen provides an index of bone matrix age. Current preclinical and clinical studies suggests that this urinary ratio provides information about bone strength and fracture risk independent of bone mineral density and that it responds differently according to the type of therapy regulating bone turnover.

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Section: What Is Bone Matrix Quality?mentioning

confidence: 99%

Section: What Is Bone Matrix Quality?mentioning

confidence: 99%

Section: What Is Bone Matrix Quality?mentioning

confidence: 99%

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Is bone quality associated with collagen age?

et al. 2009

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“…It appears likely that osteoclasts sense, via their integrin-mediated adhesions, various features of the underlying matrix, including its chemical nature, level of mineralization, local rigidity, topography and the density of adhesive ligands. For example, the resorptive activity of osteoclasts on old bone is substantially higher than that on new bone (Henriksen et al, 2007); moreover, the assembly of a sealing zone occurs on selective and confined areas within the osteoclastbone interface (Geblinger et al, 2009). Although indications for the adhesion-mediated surface sensing ability of osteoclasts are compelling, the nature of the specific bone features which are differentially sensed, and the cellular mechanisms triggered by them, are still unknown.…”

Section: Introductionmentioning

confidence: 99%

Nano-topography sensing by osteoclasts

Geblinger

Addadi

Geiger

2010

Journal of Cell Science

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Bone resorption by osteoclasts depends on the assembly of a specialized, actin-rich adhesive ‘sealing zone’ that delimits the area designed for degradation. In this study, we show that the level of roughness of the underlying adhesive surface has a profound effect on the formation and stability of the sealing zone and the associated F-actin. As our primary model substrate, we use ‘smooth’ and ‘rough’ calcite crystals with average topography values of 12 nm and 530 nm, respectively. We show that the smooth surfaces induce the formation of small and unstable actin rings with a typical lifespan of ~8 minutes, whereas the sealing zones formed on the rough calcite surfaces are considerably larger, and remain stable for more than 6 hours. It was further observed that steps or sub-micrometer cracks on the smooth surface stimulate local ring formation, raising the possibility that similar imperfections on bone surfaces may stimulate local osteoclast resorptive activity. The mechanisms whereby the physical properties of the substrate influence osteoclast behavior and their involvement in osteoclast function are discussed.

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“…The resorption of mature bone can be assessed by measuring the release of isomerized CTX (hhCTX); however, this is not as sensitive for the detection of bone metastases as aaCTX. The CTX epitope is generated by cathepsin K released by osteoclasts, thus being specific for bone resorption (11).…”

Section: Introductionmentioning

confidence: 99%

Biochemical Markers for Monitoring Response to Therapy: Evidence for Higher Bone Specificity by a Novel Marker Compared with Routine Markers

Leeming

Hegele²,

Byrjalsen³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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The aim of the present study was to compare a novel marker for high bone turnover with two routine markers for screening in prostate cancer patients. The markers were evaluated in two studies: (a) a crosssectional study of 170 prostate cancer patients with local disease stratified by Flymph node metastases (N 0 , N 1 ) compared with controls and (b) a longitudinal study of 40 hormone refractory prostate cancer patients stratified by skeletal involvement and followed during docetaxel (+/ÀBM) and zoledronate (+BM) treatment. Presence or absence of bone metastases (BM) was assessed by imaging techniques (magnetic resonance imaging or X-ray) and technetium-99m scintigraphy. The serum or urinary levels of alpha C-telopeptide of collagen type I (AACTX), prostate-specific antigen (PSA), and total alkaline phosphatase (tALP) were assessed. PSA was elevated in both N 0 and N 1 patients compared with controls, whereas AACTX was elevated only in N 1 patients. tALP exhibited no difference in any of the groups. In the treatment study, PSA decreased with treatment in both the ÀBM and +BM groups compared with baseline values, showing similar effect of docetaxel or docetaxel/zoledronate treatment on this marker. On the contrary, AACTX and tALP did not decrease with docetaxel treatment in the ÀBM group compared with baseline, whereas it decreased significantly with docetaxel/zoledronate treatment in the +BM group, already after 1 month of treatment for AACTX. Results suggest that AACTX is superior to PSA and tALP for identifying patients having a high risk of metastatic disease and for monitoring skeletal progression in +BM prostate cancer patients during treatment. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1269 -76)

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Osteoclasts prefer aged bone

Abstract: These data indicate that the age of the bone plays an important role in controlling osteoclast-mediated resorption, with significantly higher levels of osteoclast differentiation and resorption on aged bones when compared to young bones.

Cited by 67 publications

References 48 publications

Is bone quality associated with collagen age?

Is bone quality associated with collagen age?

Nano-topography sensing by osteoclasts

Biochemical Markers for Monitoring Response to Therapy: Evidence for Higher Bone Specificity by a Novel Marker Compared with Routine Markers

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