BoneKEy Reports

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ISSN / EISSN : 2047-6396 / 2047-6396
Published by: Springer Nature (10.1038)
Total articles ≅ 536
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Published: 13 January 2017
BoneKEy Reports, Volume 6; https://doi.org/10.1038/bonekey.2016.82

Abstract:
In this review, I consider the varied mechanisms in cortical bone that help preserve its integrity and how they deteriorate with aging. Aging affects cortical bone in two ways: extrinsically through its effects on the individual that modify its mechanical loading experience and “milieu interieur”; and intrinsically through the prolonged cycle of remodeling and renewal extending to an estimated 20 years in the proximal femur. Healthy femoral cortex incorporates multiple mechanisms that help prevent fracture. These have been described at multiple length scales from the individual bone mineral crystal to the scale of the femur itself and appear to operate hierarchically. Each cortical bone fracture begins as a submicroscopic crack that enlarges under mechanical load eg that imposed by a fall. In these conditions, a crack will enlarge explosively unless the cortical bone is intrinsically tough (the opposite of brittle). Toughness leads to microscopic crack deflection and bridging and may be increased by adequate regulation of both mineral crystal size and the heterogeneity of mineral and matrix phases. The role of osteocytes in optimizing toughness is beginning to be worked out; but many osteocytes die in situ without triggering bone renewal over a 20 year cycle, with potential for increasing brittleness. Furthermore, the supero-lateral cortex of the proximal femur thins progressively during life, so increasing the risk of buckling during a fall. Besides preserving or increasing hip BMD, pharmaceutical treatments have class-specific effects on the toughness of cortical bone, while dietary and exercise-based interventions show early promise
Sandra M Sacco, Caitlin Saint, Amanda B Longo, Charles B Wakefield, Phil L Salmon, Paul J Leblanc,
Published: 13 January 2017
BoneKEy Reports, Volume 6; https://doi.org/10.1038/bonekey.2016.87

Abstract:
Long-term effects of repeated i micro-computed tomography (μCT) scanning at key stages of growth and bone development (ages 2, 4 and 6 months) on trabecular and cortical bone structure, as well as developmental patterns, have not been studied. We determined the effect of repetitive μCT scanning at age 2, 4 and 6 months on tibia bone structure of male and female CD-1 mice and characterized developmental changes. At 2, 4 and 6 months of age, right tibias were scanned using μCT (Skyscan 1176) at one of three doses of radiation per scan: 222, 261 or 460 mGy. Left tibias of the same mice were scanned only at 6 months to serve as non-irradiated controls to determine whether recurrent radiation exposure alters trabecular and cortical bone structure at the proximal tibia. In males, eccentricity was lower (<0.05) in irradiated compared with non-irradiated tibias (222 mGy group). Within each sex, all other structural outcomes were similar between irradiated and non-irradiated tibias regardless of dose. Trabecular bone loss occurred in all mice due to age while cortical development continued to age 6 months. In conclusion, repetitive μCT scans at various radiation doses did not damage trabecular or cortical bone structure of proximal tibia in male and female CD-1 mice. Moreover, scanning at 2, 4 and 6 months of age highlight the different developmental time course between trabecular and cortical bone. These scanning protocols can be used to investigate longitudinal responses of bone structures to an intervention.
, Greg D Gamble, Ian R Reid
Published: 7 December 2016
BoneKEy Reports, Volume 5; https://doi.org/10.1038/bonekey.2016.85

Abstract:
Hyperparathyroidism may be associated with skeletal and cardiovascular abnormalities, but it is unclear whether these associations exist for high-normal levels of parathyroid hormone (PTH). We assessed relationships between PTH and anthropometric, skeletal and cardiometabolic indices in normal men. Body composition, blood pressure, biochemistry and bone mineral density (BMD) were evaluated in 151 healthy men. BMD was reassessed at 2 years, and coronary artery calcium (CAC) was measured at 3.5 years. Relationships between PTH and other baseline characteristics, CAC scores and change in BMD were evaluated. PTH correlated positively with baseline body mass index, fat mass, diastolic blood pressure, triglycerides, total and low-density lipoprotein (LDL) cholesterol, (r=0.19–0.25, P=0.02–0.002), and with category of CAC score. Relationships between PTH and cardiometabolic indices remained significant after adjustment for age, 25-hydroxyvitamin D and estimated glomerular filteration rate. Men in the top PTH tertile (⩾4.4 pmol l−1, n=51) were more likely to have LDL cholesterol ⩾3.5 mmol l−1, diastolic blood pressure ⩾85 mm Hg, and CAC score >0 than men in lower tertiles. PTH was not associated with history of fracture, baseline BMD, or change in BMD over 2 years. In summary, in this cohort of healthy men, PTH levels are linearly related to adiposity and to cardiometabolic indices, but not to BMD or bone loss. These findings suggest that adiposity should be considered as an independent cause of secondary hyperparathyroidism, and they may be relevant to patients with normocalcemic hyperparathyroidism, in whom high PTH levels may be a marker of adiposity and cardiometabolic risk rather than always indicating parathyroid autonomy.
Published: 7 December 2016
BoneKEy Reports, Volume 5; https://doi.org/10.1038/bonekey.2016.86

Abstract:
The high incidence of secondary hip fractures and the associated markedly increased mortality call for preventive actions that could help to avoid these injuries. By providing immediate strengthening and not relying on patient compliance, internal prophylactic augmentation of the osteoporotic proximal femur may overcome the main limitations of systemic bone drugs and wearable protective pads. However, such a method would have to provide sufficient and reliable strengthening effect with minimal risks and side effects to justify the need of an invasive treatment. The requirements for an internal reinforcement approach are thus strict and include mechanical, biological, clinical, ethical and financial criteria. Here we first attempt to describe the properties of an ideal augmentation method. Previously published methodologies and techniques developed at our research institute, including approaches using cements, metals, other materials or combined approaches, are then reviewed and evaluated according to these aspects. We conclude that none of the discussed methodologies appears to be able to deliver a sufficiently high gain-versus-risk ratio that could justify the clinical application and thus augmentation of the osteoporotic proximal femur remains a challenge. Finally, we provide suggestions for the development and evaluation of future strategies.
Gloria Allocca, Anjali P Kusumbe, ,
Published: 7 December 2016
BoneKEy Reports, Volume 5; https://doi.org/10.1038/bonekey.2016.84

Abstract:
Confocal and two-photon microscopy has been widely used in bone research to not only produce high quality, three-dimensional images but also to provide valuable structural and quantitative information. In this article, we describe step-by-step protocols for confocal and two-photon microscopy to investigate earlier cellular events during colonisation of cancer cells in bone using xenograft mouse models. This includes confocal/two-photon microscopy imaging of paraformaldehyde fixed thick bone sections and frozen bone samples.
, Nicole Y C Yu, Iman Jalilian, André F Pereira, Ulf R Knothe
Published: 30 November 2016
BoneKEy Reports, Volume 5; https://doi.org/10.1038/bonekey.2016.70

Abstract:
Periosteum is a smart mechanobiological material that serves as a habitat and delivery vehicle for stem cells as well as biological factors that modulate tissue genesis and healing. Periosteum's remarkable regenerative capacity has been harnessed clinically for over two hundred years. Scientific studies over the past decade have begun to decipher the mechanobiology of periosteum, which has a significant role in its regenerative capacity. This integrative review outlines recent mechanobiological insights that are key to modulating and translating periosteum and its resident stem cells in a regenerative medicine context.
, Jeffrey L Price
Published: 16 November 2016
BoneKEy Reports, Volume 5; https://doi.org/10.1038/bonekey.2016.80

Abstract:
Deletion of proprotein convertase Mbtps1 in bone osteocytes leads to a significant postnatal increase in skeletal muscle size and contractile function, while causing only a 25% increase in stiffness in long bones. Concerns about leakiness in skeletal muscle were discounted since Cre recombinase expression does not account for our findings, and, Mbtps1 protein and mRNA is not deleted. Interestingly, the response of normal skeletal muscle to exercise and the regenerative response of skeletal muscle to the deletion of Mbtps1 in bone share some key regulatory features including a preference for slow twitch muscle fibers. In addition, transcriptional regulators PPAR, PGC-1α, LXR, and repressors DEC1 and DEC2 all occupy central positions within these two pathways. We hypothesize that the age-dependent muscle phenotype in Dmp1-Cre Mbtps1 cKO mice is due to bone→muscle crosstalk. Many of the myogenic genes altered in this larger and functionally improved muscle are regulated by circadian core transcriptional repressors DEC1 and DEC2, and furthermore, display a temporal coordination with Dec1 and Dec2 expression consistent with a regulatory co-dependency. These considerations lead us to propose that Dmp1-Cre Mbtps1 cKO osteocytes activate myogenesis by increased release of an activator of muscle PPAR-gamma, for example, PGE2 or sphingosine-1-P, or, by diminished release of an inhibitor of LXR, for example, long-chain polyunsaturated fatty acids. We hope that further investigation of these interacting pathways in the Dmp1-Cre Mbtps1 cKO model will lead to clinically translatable findings applicable to age-related sarcopenia and other muscle wasting syndromes.
Sandeep Paul,
Published: 16 November 2016
BoneKEy Reports, Volume 5; https://doi.org/10.1038/bonekey.2016.81

Abstract:
BoneKEy is an online knowledge resource providing coverage of the field of bone and mineral metabolism. Covering both basic science research and clinical investigations, BoneKEy will provide the bone field with an online platform for scientific exchange and community growth based on expert scientific content
Elizabeth Rendina-Ruedy,
Published: 26 October 2016
BoneKEy Reports, Volume 5; https://doi.org/10.1038/bonekey.2016.71

Abstract:
The prevalence of obesity and type 2 diabetes mellitus (T2DM) continues to rise, and as a result, research aimed at understanding the molecular basis for the co-morbidities has become an area of much scientific interest. Among the more recently recognized chronic complications of T2DM is the increased risk of fracture, especially hip fracture, that has been reported independent of bone mineral density (BMD). A widely used animal model to study how the development and progression of impaired glucose tolerance affect the skeleton has been the diet-induce obesity (DIO) model. As the name implies, this model employs the use of a version of high-fat diets to induce obesity and the subsequent metabolic perturbations that occur with T2DM. Although the model offers a number of advantages, the literature reveals some inconsistent results. Upon further review, discrepancies in the choice of the experimental high-fat diets and the control diets have become a point of major concern. The variability between diets and study design has made it difficult to compare data and results across studies. Therefore, this review aims to provide guidelines that should be employed when designing studies using DIO models of T2DM.
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