Altered bone composition in children with vertebral fracture

Authors

Inari S Tamminen, Mervi K Mäyränpää, Mikael J Turunen, Hanna Isaksson, Outi Mäkitie, Jukka S Jurvelin, Heikki Kröger

Abstract

Primary osteoporosis in children often leads to vertebral fractures but it remains unknown whether these fractures associate with changes in bone composition. This study aimed to determine the differences in bone composition in fracture-prone children with and without vertebral fractures, as assessed by Fourier transform infrared spectroscopic imaging (FTIRI) and bone histomorphometry. Iliac crest bone biopsies (n = 24) were obtained from children who were suspected of primary osteoporosis based on evidence from the fracture history and/or low bone mineral density (BMD) in DXA. Vertebral morphology was determined by radiography. Bone biopsies were analyzed using histomorphometry and FTIRI. Phosphate-to-amide I, carbonate-to-phosphate, carbonate-to-amide I, and cross-link ratios (collagen maturity) were calculated. Children with (n = 14) and without (n = 10) vertebral fracture were compared. Low cancellous bone volume (BV/TV) was detected by histomorphometry in 36% of the children with vertebral fracture, and bone turnover rate was abnormal in 64% of them. Children with vertebral fractures had lower carbonate-to-phosphate ratio (p < 0.05) and higher collagen maturity (p < 0.05) than children without vertebral fracture. The children with low BV/TV in biopsy showed lower carbonate-to-amide I ratio (p < 0.05) than the children with normal bone volume. This study showed changes in bone composition among fracture-prone children who had sustained a vertebral fracture. The observed changes in bone composition in these children might contribute to their greater propensity to sustain vertebral fractures.

Link to Article

http://dx.doi.org/10.1002/jbmr.409

NIK Stabilization in Osteoclasts Results in Osteoporosis and Enhanced Inflammatory Osteolysis

Authors

Chang Yang, Kathleen McCoy, Jennifer L. Davis, Marc Schmidt-Supprian, Yoshiteru Sasaki, Roberta Faccio, Deborah Veis Novack

Abstract

Maintenance of healthy bone requires the balanced activities of osteoclasts (OCs), which resorb bone, and osteoblasts, which build bone. Disproportionate action of OCs is responsible for the bone loss associated with postmenopausal osteoporosis and rheumatoid arthritis. NF-κB inducing kinase (NIK) controls activation of the alternative NF-κB pathway, a critical pathway for OC differentiation. Under basal conditions, TRAF3-mediated NIK degradation prevents downstream signaling, and disruption of the NIK:TRAF3 interaction stabilizes NIK leading to constitutive activation of the alternative NF-κB pathway. Using transgenic mice with OC-lineage expression of NIK lacking its TRAF3 binding domain (NT3), we now find that alternative NF-κB activation enhances not only OC differentiation but also OC function. Activating NT3 with either lysozyme M Cre or cathepsinK Cre causes high turnover osteoporosis with increased activity of OCs and osteoblasts. In vitro, NT3-expressing precursors form OCs more quickly and at lower doses of RANKL. When cultured on bone, they exhibit larger actin rings and increased resorptive activity. OC-specific NT3 transgenic mice also have an exaggerated osteolytic response to the serum transfer model of arthritis. Constitutive activation of NIK drives enhanced osteoclastogenesis and bone resorption, both in basal conditions and in response to inflammatory stimuli.

Link to Article

http://dx.doi.org/10.1371/journal.pone.0015383

NIK Stabilization in Osteoclasts Results in Osteoporosis and Enhanced Inflammatory Osteolysis

Authors

Chang Yang, Kathleen McCoy, Jennifer L. Davis, Marc Schmidt-Supprian, Yoshiteru Sasaki, Roberta Faccio, Deborah Veis Novack

Abstract

Background: Maintenance of healthy bone requires the balanced activities of osteoclasts (OCs), which resorb bone, and osteoblasts, which build bone. Disproportionate action of OCs is responsible for the bone loss associated with postmenopausal osteoporosis and rheumatoid arthritis. NF-B inducing kinase (NIK) controls activation of the alternative NF-B pathway, a critical pathway for OC differentiation. Under basal conditions, TRAF3-mediated NIK degradation prevents downstream signaling, and disruption of the NIK:TRAF3 interaction stabilizes NIK leading to constitutive activation of the alternative NF-B pathway. Methodology/Principal Findings: Using transgenic mice with OC-lineage expression of NIK lacking its TRAF3 binding domain (NT3), we now find that alternative NF-B activation enhances not only OC differentiation but also OC function. Activating NT3 with either lysozyme M Cre or cathepsinK Cre causes high turnover osteoporosis with increased activity of OCs and osteoblasts. In vitro, NT3-expressing precursors form OCs more quickly and at lower doses of RANKL. When cultured on bone, they exhibit larger actin rings and increased resorptive activity. OC-specific NT3 transgenic mice also have an exaggerated osteolytic response to the serum transfer model of arthritis. Conclusions: Constitutive activation of NIK drives enhanced osteoclastogenesis and bone resorption, both in basal conditions and in response to inflammatory stimuli.

Link to Article

http://dx.doi.org/10.1371/journal.pone.0015383

Influence of Different-Frequency GlucocorticoidInduction on Morphological Structures of Humeri,Soft Tissues and Immune System in Rats

Authors

Li Jian-min, Li Heng

Abstract

Objective: To explore the influence of different-frequency glucocorticoid (GC) induction on morphological structures of humeri and soft tissues as well as immune system in rats. 

Methods: A total of 32 specific pathogen-free (SPF) SD rats at the age of 3 months were selected and randomly divided into 4 groups, 8 cases in each group. The rats in control group were not given any treatment, while those in low-, moderate- and high-frequency groups were treated with intramuscular injection of dexamethasone 1 mg/kg per time for twice, 4 times and 6 times per week, respectively. All the rats were sacrificed on d30 to measure their body mass and qualities of soft tissues and immune organs, and bone histomorphometry was applied to analyze humeral bone mass and bone structural changes.

Results: Compared with control group, there was no change in cancellous bone mass and bone structures of upper humeri in low-frequency group, but serious loss of bone mass, significantly degenerated bone structure, markedly reduced trabecular thickness and number as well as notably increased trabecular separation was all observed in moderate- and high-frequency groups. The size of cortical bones, total size of bone structure, thickness of cortical bones and size percentage of cortical bones in middle humeri reduced apparently, while the size percentage of medullary cavity increased dramatically in high-frequency group. Growth plate thickness of upper humeri decreased in low-, moderate- and high-frequency groups, and the diameters of mastocytes diminished in moderate- and high-frequency groups. Compared with control group, body mass decreased obviously, qualities and indexes of spleen and thymus showed decreasing tendency along with the increase of drug administration frequency in low-, moderate- and high-frequency groups.

Conclusion: Low-frequency GC cannot change humeral morphology. The higher the frequency of drug administration is, the more the loss of cancellous bone mass is. When the frequency reaches to 6 times per week, the loss of cortical and cancellous bones is much severer. However, with the increase of drug administration frequency, thymic degeneration, splenic atrophy and immunosuppression can be induced. Therefore, the influence of different-frequency drug administration on bones and soft tissues in different locations as well as immune function should be fully considered and reasonable drug administration protocols should be designed for the establishment of SD rat models with osteoporosis.

Link to Article

http://scholar.google.com/scholar_url?url=http://www.jitm.hk/CN/article/downloadArticleFile.do%3FattachType%3DPDF%26id%3D196&hl=en&sa=X&scisig=AAGBfm28q6Urn7yc_UONqiUYfhESjzbqFA&nossl=1&oi=scholaralrt

Co-administration of aspirin and allogeneic adipose-derived stromal cells attenuates bone loss in ovariectomized rats through the anti-inflammatory and chemotactic abilities of aspirin

Authors

Hao Liu, Wei Li, Yunsong Liu, Xiao Zhang and Yongsheng Zhou

Abstract

Introduction
Osteoporosis is a syndrome of excessive skeletal fragility characterized by the loss of mass and deterioration of microarchitecture in bone. Single use of aspirin or adipose-derived stromal cells (ASCs) has been recognized recently to be effective against osteoporosis. The goal of the study was to evaluate the osteogenic effects of the co-administration of aspirin and allogeneic rat adipose-derived stromal cells (rASCs) on ovariectomized (OVX)-induced bone loss in rats. The underlying mechanisms were investigated in vitro and in vivo.

Methods
Firstly, allogeneic rASCs were isolated and cultured, and the conditioned medium (CM) from the maintenance of rASCs was collected. Secondly, the OVX rats were administrated CM, rASCs, aspirin (ASP) or rASCs + ASP, respectively. Twelve weeks later, the anti-inflammatory and osteogenic effects were assessed by micro-CT, undecalcified histological sections, dynamic histomorphometric analyses and serologic assays for biochemical markers. Finally, a Transwell migration assay in vitro and cell-trafficking analyses in vivo were used to explore the effects of aspirin on rASC migration.

Results
Systemic administration of aspirin and rASCs attenuated OVX-induced bone loss better than single use of aspirin or ASCs (p < 0.05, respectively). Next, we analyzed the underlying mechanisms of the anti-inflammatory and chemotactic abilities of aspirin. Aspirin suppressed serum levels of the pro-inflammatory cytokines on tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and the anti-inflammatory ability was positively associated with bone morphometry. Also, aspirin exhibited excellent chemotactic effects in vitro and accelerated the homing of allogeneic rASCs into bone marrow during early in vivo stages.

Conclusions
Co-administered aspirin and allogeneic ASCs can partially reverse OVX-induced bone loss in rats. This effect appears to be mediated by the anti-inflammatory and chemotactic abilities of aspirin.

Link to Article

http://dx.doi.org/10.1186/s13287-015-0195-x