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Article: Dose-dependent effects of pharmaceutical treatments on bone matrix properties in ovariectomized rats.

Karim, Lamya / Kwaczala, Andrea / Vashishth, Deepak / Judex, Stefan

2021 Volume 15, Page(s) 101137

Abstract: As both anabolic and anti-catabolic osteoporosis drugs affect bone formation and resorption processes, they may contribute to bone's overall mechanical behavior by altering the quality of the bone matrix. We used an ovariectomized rat model and a novel ... ...

Abstract	As both anabolic and anti-catabolic osteoporosis drugs affect bone formation and resorption processes, they may contribute to bone's overall mechanical behavior by altering the quality of the bone matrix. We used an ovariectomized rat model and a novel fracture mechanics approach to investigate whether treatment with an anabolic (parathyroid hormone) or anti-catabolic (alendronate) osteoporosis drugs will alter the organic and mineral matrix components and consequently cortical bone fracture toughness. Ovariectomized (at 5 months age) rats were treated with either parathyroid hormone or alendronate at low and high doses for 6 months (age 6-12 months). Specifically, treatment groups included untreated ovariectomized controls (n = 9), high-dose alendronate (n = 10), low-dose alendronate (n = 9), high-dose parathyroid hormone (n = 10), and low-dose parathyroid hormone (n = 9). After euthanasia, cortical microbeams from the lateral quadrant were extracted, notched, and tested in 3-point bending to measure fracture toughness. Portions of the bone were used to measure changes in the 1) organic matrix through quantification of advanced glycation end-products (AGEs) and non-collagenous proteins, and 2) mineral matrix through assessment of mineral crystallinity. Compared to the ovariectomized group, rats treated with high doses of parathyroid hormone and alendronate had significantly increased cortical bone fracture toughness, which corresponded primarily to increased non-collagenous proteins while there was no change in AGEs. Additionally, low-dose PTH treatment increased matrix crystallinity and decreased AGE levels. In summary, ovariectomized rats treated with pharmaceutical drugs had increased non-collagenous matrix proteins and improved fracture toughness compared to controls. Further investigation is required for different doses and longer treatment periods.
Language	English
Publishing date	2021-10-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2821774-3
ISSN	2352-1872
ISSN	2352-1872
DOI	10.1016/j.bonr.2021.101137
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Article: Differential Efficacy of 2 Vibrating Orthodontic Devices to Alter the Cellular Response in Osteoblasts, Fibroblasts, and Osteoclasts.

Judex, Stefan / Pongkitwitoon, Suphannee

Dose-response : a publication of International Hormesis Society

2018 Volume 16, Issue 3, Page(s) 1559325818792112

Abstract: Modalities that increase the rate of tooth movement have received considerable attention, but direct comparisons between devices are rare. Here, we contrasted 2 mechanical vibratory devices designed to directly transfer vibrations into alveolar bone as a ...

Abstract	Modalities that increase the rate of tooth movement have received considerable attention, but direct comparisons between devices are rare. Here, we contrasted 2 mechanical vibratory devices designed to directly transfer vibrations into alveolar bone as a means to influence bone remodeling. To this end, 3 cells types intimately involved in modulating tooth movements-osteoblasts, periodontal ligament fibroblasts, and osteoclasts-were subjected to in vitro vibrations at bout durations prescribed by the manufacturers. As quantified by an accelerometer, vibration frequency and peak accelerations were 400% and 70% greater in the VPro5 (Propel Orthodontics) than in the AcceleDent (OrthoAccel Technologies) device. Both devices caused increased cell proliferation and gene expression in osteoblasts and fibroblasts, but the response to VPro5 treatment was greater than for the AcceleDent. In contrast, the ability to increase osteoclast activity was device independent. These data present an important first step in determining how specific cell types important for facilitating tooth movement respond to different vibration profiles. The device that engendered a higher vibration frequency and larger acceleration (VPro5) was superior in stimulating osteoblast and fibroblast cell proliferation/gene expression, although the duration of each treatment bout was 75% shorter than for the AcceleDent.
Language	English
Publishing date	2018-08-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2440820-7
ISSN	1559-3258 ; 1559-3258
ISSN (online)	1559-3258
ISSN	1559-3258
DOI	10.1177/1559325818792112
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Article ; Online: Modeling stem cell nucleus mechanics using confocal microscopy.

Kennedy, Zeke / Newberg, Joshua / Goelzer, Matthew / Judex, Stefan / Fitzpatrick, Clare K / Uzer, Gunes

Biomechanics and modeling in mechanobiology

2021 Volume 20, Issue 6, Page(s) 2361–2372

Abstract: Nuclear mechanics is emerging as a key component of stem cell function and differentiation. While changes in nuclear structure can be visually imaged with confocal microscopy, mechanical characterization of the nucleus and its sub-cellular components ... ...

Abstract	Nuclear mechanics is emerging as a key component of stem cell function and differentiation. While changes in nuclear structure can be visually imaged with confocal microscopy, mechanical characterization of the nucleus and its sub-cellular components require specialized testing equipment. A computational model permitting cell-specific mechanical information directly from confocal and atomic force microscopy of cell nuclei would be of great value. Here, we developed a computational framework for generating finite element models of isolated cell nuclei from multiple confocal microscopy scans and simple atomic force microscopy (AFM) tests. Confocal imaging stacks of isolated mesenchymal stem cells were converted into finite element models and siRNA-mediated Lamin A/C depletion isolated chromatin and Lamin A/C structures. Using AFM-measured experimental stiffness values, a set of conversion factors were determined for both chromatin and Lamin A/C to map the voxel intensity of the original images to the element stiffness, allowing the prediction of nuclear stiffness in an additional set of other nuclei. The developed computational framework will identify the contribution of a multitude of sub-nuclear structures and predict global nuclear stiffness of multiple nuclei based on simple nuclear isolation protocols, confocal images and AFM tests.
MeSH term(s)	Animals ; Cell Nucleus/metabolism ; Chromatin/metabolism ; Elasticity ; Lamin Type A/metabolism ; Male ; Mice, Inbred C57BL ; Microscopy, Atomic Force ; Microscopy, Confocal ; Models, Biological ; RNA, Small Interfering/metabolism ; Stem Cells/cytology ; Mice
Chemical Substances	Chromatin ; Lamin Type A ; RNA, Small Interfering
Language	English
Publishing date	2021-08-23
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2093052-5
ISSN	1617-7940 ; 1617-7959
ISSN (online)	1617-7940
ISSN	1617-7959
DOI	10.1007/s10237-021-01513-w
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Zs.A 5966: Show issues

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Article ; Online: Low-Intensity Vibration Protects the Weight-Bearing Skeleton and Suppresses Fracture Incidence in Boys With Duchenne Muscular Dystrophy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Bianchi, Maria Luisa / Vai, Silvia / Baranello, Giovanni / Broggi, Francesca / Judex, Stefan / Hangartner, Thomas / Rubin, Clinton

JBMR plus

2022 Volume 6, Issue 11, Page(s) e10685

Abstract: The ability of low-intensity vibration (LIV) to combat skeletal decline in Duchenne Muscular Dystrophy (DMD) was evaluated in a randomized controlled trial. Twenty DMD boys were enrolled, all ambulant and treated with glucocorticoids (mean age 7.6, ... ...

Abstract	The ability of low-intensity vibration (LIV) to combat skeletal decline in Duchenne Muscular Dystrophy (DMD) was evaluated in a randomized controlled trial. Twenty DMD boys were enrolled, all ambulant and treated with glucocorticoids (mean age 7.6, height-adjusted
Language	English
Publishing date	2022-10-18
Publishing country	England
Document type	Clinical Trial
ISSN	2473-4039
ISSN (online)	2473-4039
DOI	10.1002/jbm4.10685
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Article ; Online: Differences in bone structure and unloading-induced bone loss between C57BL/6N and C57BL/6J mice.

Sankaran, Jeyantt S / Varshney, Manasvi / Judex, Stefan

Mammalian genome : official journal of the International Mammalian Genome Society

2017 Volume 28, Issue 11-12, Page(s) 476–486

Abstract: The C57BL/6 mouse, the most frequently utilized animal model in biomedical research, is in use as several substrains, all of which differ by a small array of genomic differences. Two of these substrains, C57BL/6J (B6J) and C57BL/6N (B6N), are commonly ... ...

Abstract	The C57BL/6 mouse, the most frequently utilized animal model in biomedical research, is in use as several substrains, all of which differ by a small array of genomic differences. Two of these substrains, C57BL/6J (B6J) and C57BL/6N (B6N), are commonly used but it is unclear how phenotypically similar or different they are. Here, we tested whether adolescent B6N mice have a bone phenotype and respond to the loss of weightbearing differently than B6J. At 9 weeks of age, normally ambulating B6N had lower trabecular bone volume fraction but greater bone formation rates and osteoblast surfaces than corresponding B6J. At 11 weeks of age, differences in trabecular indices persisted between the substrains but differences in cellular activity had ceased. Cortical bone indices were largely similar between the two substrains. Hindlimb unloading (HLU) induced similar degeneration of trabecular architecture and cellular activity in both substrains when comparing 11-week-old HLU mice to 11-week-old controls. However, unloaded B6N mice had smaller cortices than B6J. When comparing HLU to 9 weeks baseline control mice, deterioration in trabecular separation, osteoblast indices, and endocortical variables was significantly greater in B6N than B6J. These data indicate specific developmental differences in bone formation and morphology between B6N and B6J mice, giving rise to a differential response to mechanical unloading that may be modulated, in part, by the genes Herc2, Myo18b, and Acan. Our results emphasize that these substrains cannot be used interchangeably at least for investigations in which the phenotypic makeup and its response to extraneous stimuli are of interest.
MeSH term(s)	Animals ; Bone and Bones/physiology ; Disease Models, Animal ; Female ; Hindlimb Suspension/methods ; Mice ; Mice, Inbred C57BL ; Osteogenesis/physiology ; Phenotype
Language	English
Publishing date	2017-12
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1058547-3
ISSN	1432-1777 ; 0938-8990
ISSN (online)	1432-1777
ISSN	0938-8990
DOI	10.1007/s00335-017-9717-4
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Zs.A 3489: Show issues

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Article ; Online: Trabecular bone recovers from mechanical unloading primarily by restoring its mechanical function rather than its morphology.

Ozcivici, Engin / Judex, Stefan

Bone

2014 Volume 67, Page(s) 122–129

Abstract: Upon returning to normal ambulatory activities, the recovery of trabecular bone lost during unloading is limited. Here, using a mouse population that displayed a large range of skeletal susceptibility to unloading and reambulation, we tested the impact ... ...

Abstract	Upon returning to normal ambulatory activities, the recovery of trabecular bone lost during unloading is limited. Here, using a mouse population that displayed a large range of skeletal susceptibility to unloading and reambulation, we tested the impact of changes in trabecular bone morphology during unloading and reambulation on its simulated mechanical properties. Female adult mice from a double cross of BALB/cByJ and C3H/HeJ strains (n=352) underwent 3wk of hindlimb unloading followed by 3wk of reambulation. Normally ambulating mice served as controls (n=30). As quantified longitudinally by in vivo μCT, unloading led to an average loss of 43% of trabecular bone volume fraction (BV/TV) in the distal femur. Finite element models of the μCT tomographies showed that deterioration of the trabecular structure raised trabecular peak Von-Mises (PVM) stresses on average by 27%, indicating a significant increase in the risk of mechanical failure compared to baseline. Further, skewness of the Von-Mises stress distributions (SVM) increased by 104% with unloading, indicating that the trabecular structure became inefficient in resisting the applied load. During reambulation, bone of experimental mice recovered on average only 10% of its lost BV/TV. Even though the addition of trabecular tissue was small during reambulation, PVM and SVM as indicators of risk of mechanical failure decreased by 56% and 57%, respectively. Large individual differences in the response of trabecular bone, together with a large sample size, facilitated stratification of experimental mice based on the level of recovery. As a fraction of all mice, 66% of the population showed some degree of recovery in BV/TV while in 89% and 87% of all mice, PVM and SVM decreased during reambulation, respectively. At the end of the reambulation phase, only 8% of the population recovered half of the unloading induced losses in BV/TV while 50% and 49% of the population recovered half of the unloading induced deterioration in PVM and SVM, respectively. The association between morphological and mechanical variables was strong at baseline but progressively decreased during the unloading and reambulation cycles. The preferential recovery of trabecular micromechanical properties over bone volume fraction emphasizes that mechanical demand during reambulation does not, at least initially, seek to restore bone's morphology but its mechanical integrity.
MeSH term(s)	Animals ; Bone and Bones/physiology ; Female ; Finite Element Analysis ; Hindlimb Suspension/physiology ; Mice
Language	English
Publishing date	2014-10
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
DOI	10.1016/j.bone.2014.05.009
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Zs.A 1571: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 332: Show issues

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Article ; Online: Low level irradiation in mice can lead to enhanced trabecular bone morphology.

Karim, Lamya / Judex, Stefan

Journal of bone and mineral metabolism

2013 Volume 32, Issue 5, Page(s) 476–483

Abstract: Charged particle radiation such as iron ions and their secondary fragmentation products are of particular concern to the skeleton due to their high charge and energy deposition. However, little is known about the long-term effects of these particles on ... ...

Abstract	Charged particle radiation such as iron ions and their secondary fragmentation products are of particular concern to the skeleton due to their high charge and energy deposition. However, little is known about the long-term effects of these particles on trabecular and cortical bone morphology when applied at relatively low levels. We hypothesized that even a 4.4 cGy dose of a complex secondary iron ion radiation field will compromise skeletal quantity and architecture in adult mice. One year after radiation exposure and compared to age-matched controls, 4.4 cGy irradiated mice had 51 % more trabecular bone, 56 % greater trabecular bone volume fraction, 16 % greater trabecular number, and 17 % less trabecular separation in the distal metaphysis of the femur. Similar to the metaphysis, trabecular bone of the distal femoral epiphysis in 4.4 cGy mice had 33 % more trabecular bone, 31 % greater trabecular bone volume fraction, and a 33 % smaller structural model index. Cortical bone morphology, whole bone mechanical properties, and lower leg muscle mass were unaffected. When compared to two additional groups, irradiated at either 8.9 or 17.8 cGy, a (negative) dose response relationship was observed for trabecular bone in the metaphysis but not in the epiphysis. In contrast to our original hypothesis, these data indicated that a secondary field of low-level, high-linear energy transfer iron radiation may cause long-term augmentation, rather than deterioration, of trabecular bone in the femoral metaphysis and epiphysis of mice.
MeSH term(s)	Animals ; Bone and Bones/anatomy & histology ; Bone and Bones/diagnostic imaging ; Bone and Bones/radiation effects ; Epiphyses/diagnostic imaging ; Epiphyses/radiation effects ; Male ; Mice, Inbred C57BL ; Radiation, Ionizing ; X-Ray Microtomography
Language	English
Publishing date	2013-10-11
Publishing country	Japan
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1295123-7
ISSN	1435-5604 ; 0914-8779
ISSN (online)	1435-5604
ISSN	0914-8779
DOI	10.1007/s00774-013-0518-x
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Zs.A 4894: Show issues

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Article ; Online: Cytoskeletal Configuration Modulates Mechanically Induced Changes in Mesenchymal Stem Cell Osteogenesis, Morphology, and Stiffness.

Pongkitwitoon, Suphannee / Uzer, Gunes / Rubin, Janet / Judex, Stefan

Scientific reports

2016 Volume 6, Page(s) 34791

Abstract: Mesenchymal stem cells (MSC) responding to mechanical cues generated by physical activity is critical for skeletal development and remodeling. Here, we utilized low intensity vibrations (LIV) as a physiologically relevant mechanical signal and ... ...

Abstract	Mesenchymal stem cells (MSC) responding to mechanical cues generated by physical activity is critical for skeletal development and remodeling. Here, we utilized low intensity vibrations (LIV) as a physiologically relevant mechanical signal and hypothesized that the confined cytoskeletal configuration imposed by 2D culture will enable human bone marrow MSCs (hBMSC) to respond more robustly when LIV is applied in-plane (horizontal-LIV) rather than out-of-plane (vertical-LIV). All LIV signals enhanced hBMSC proliferation, osteogenic differentiation, and upregulated genes associated with cytoskeletal structure. The cellular response was more pronounced at higher frequencies (100 Hz vs 30 Hz) and when applied in the horizontal plane. Horizontal but not vertical LIV realigned the cell cytoskeleton, culminating in increased cell stiffness. Our results show that applying very small oscillatory motions within the primary cell attachment plane, rather than perpendicular to it, amplifies the cell's response to LIV, ostensibly facilitating a more effective transfer of intracellular forces. Transcriptional and structural changes in particular with horizontal LIV, together with the strong frequency dependency of the signal, emphasize the importance of intracellular cytoskeletal configuration in sensing and responding to high-frequency mechanical signals at low intensities.
MeSH term(s)	Actinin/genetics ; Adult ; Cadherins/genetics ; Cell Culture Techniques ; Cell Differentiation ; Cell Proliferation ; Cytoskeleton/physiology ; Female ; Gene Expression Regulation ; Humans ; Mesenchymal Stromal Cells/chemistry ; Mesenchymal Stromal Cells/physiology ; Microfilament Proteins/genetics ; Microscopy, Atomic Force ; Nerve Tissue Proteins/genetics ; Nuclear Proteins/genetics ; Osteogenesis/physiology ; Vibration
Chemical Substances	ACTN1 protein, human ; Cadherins ; Microfilament Proteins ; Nerve Tissue Proteins ; Nuclear Proteins ; SYNE2 protein, human ; Actinin (11003-00-2) ; osteoblast cadherin (156621-71-5)
Language	English
Publishing date	2016--06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep34791
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Article ; Online: Trabecular and Cortical Bone of Growing C3H Mice Is Highly Responsive to the Removal of Weightbearing.

Li, Bing / Sankaran, Jeyantt Srinivas / Judex, Stefan

PloS one

2016 Volume 11, Issue 5, Page(s) e0156222

Abstract: Genetic make-up strongly influences the skeleton's susceptibility to the loss of weight bearing with some inbred mouse strains experiencing great amounts of bone loss while others lose bone at much smaller rates. At young adulthood, female inbred C3H/HeJ ...

Abstract	Genetic make-up strongly influences the skeleton's susceptibility to the loss of weight bearing with some inbred mouse strains experiencing great amounts of bone loss while others lose bone at much smaller rates. At young adulthood, female inbred C3H/HeJ (C3H) mice are largely resistant to catabolic pressure induced by unloading. Here, we tested whether the depressed responsivity to unloading is inherent to the C3H genetic make-up or whether a younger age facilitates a robust skeletal response to unloading. Nine-week-old, skeletally immature, female C3H mice were subjected to 3wk of hindlimb unloading (HLU, n = 12) or served as normal baseline controls (BC, n = 10) or age-matched controls (AC, n = 12). In all mice, cortical and trabecular architecture of the femur, as well as levels of bone formation and resorption, were assessed with μCT, histomorphometry, and histology. Changes in bone marrow progenitor cell populations were determined with flow cytometry. Following 21d of unloading, HLU mice had 52% less trabecular bone in the distal femur than normal age-matched controls. Reflecting a loss of trabecular tissue compared to baseline controls, trabecular bone formation rates (BFR/BS) in HLU mice were 40% lower than in age-matched controls. Surfaces undergoing osteoclastic resorption were not significantly different between groups. In the mid-diaphysis, HLU inhibited cortical bone growth leading to 14% less bone area compared to age-matched controls. Compared to AC, BFR/BS of HLU mice were 53% lower at the endo-cortical surface and 49% lower at the periosteal surface of the mid-diaphysis. The enriched osteoprogenitor cell population (OPC) comprised 2% of the bone marrow stem cells in HLU mice, significantly different from 3% OPC in the AC group. These data show that bone tissue in actively growing C3H mice is lost rapidly, or fails to grow, during the removal of functional weight bearing-in contrast to the insignificant response previously demonstrated in female young adult C3H mice. Thus, the attributed low sensitivity of the C3H mouse strain to the loss of mechanical signals is not apparent at a young age and this trait therefore does not reflect a genetic regulation throughout the life span of this strain. These results highlight the significance of age in modulating the contribution of genetics in orchestrating bone's response to unloading and that the skeletal unresponsiveness of young adult C3H mice to the loss of weight bearing is not genetically hard-wired.
MeSH term(s)	Animals ; Bone Development ; Cancellous Bone/diagnostic imaging ; Cancellous Bone/physiopathology ; Cortical Bone/diagnostic imaging ; Cortical Bone/physiopathology ; Female ; Hindlimb Suspension/methods ; Mesenchymal Stem Cells/cytology ; Mice ; Mice, Inbred C3H ; Weight-Bearing ; X-Ray Microtomography/methods
Language	English
Publishing date	2016-05-25
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0156222
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Article ; Online: Diets High in Fat or Fructose Differentially Modulate Bone Health and Lipid Metabolism.

Jatkar, Aditi / Kurland, Irwin J / Judex, Stefan

Calcified tissue international

2016 Volume 100, Issue 1, Page(s) 20–28

Abstract: Diets high in fat or carbohydrates can lead to obesity and diabetes, two interrelated conditions that have been associated with osteoporosis. Here, we contrasted the effects of a high fat (HF) versus fructose-enriched carbohydrate (CH) versus regular ... ...

Abstract	Diets high in fat or carbohydrates can lead to obesity and diabetes, two interrelated conditions that have been associated with osteoporosis. Here, we contrasted the effects of a high fat (HF) versus fructose-enriched carbohydrate (CH) versus regular chow (SC) diet on bone morphology, fat content and metabolic balance in BALB/cByJ mice over a 15-week period. For 13 weeks, there were no differences in body mass between groups with small differences in the last 2 weeks. Even without the potentially confounding factor of altered body mass and levels of load bearing, HF consumption was detrimental to bone in the distal femur with lower trabecular bone volume fraction and thinner cortices than controls. These differences in bone were accompanied by twofold greater abdominal fat content and fourfold greater plasma leptin concentrations. High-fat feeding caused a decrease in de-novo lipid synthesis in the liver, kidney, white adipose and brown adipose tissue. In contrast to HF, the fructose diet did not significantly impact bone quantity or architecture. Fructose consumption also did not significantly alter leptin levels or de-novo lipid synthesis but reduced epididymal adipose tissue and increased brown adipose tissue. Cortical stiffness was lower in the CH than in HF mice. There were no differences in glucose or insulin levels between groups. Together, a diet high in fat had a negative influence on bone structure, adipose tissue deposition and lipid synthesis, changes that were largely avoided with a fructose-enriched diet.
MeSH term(s)	Adipose Tissue/metabolism ; Animals ; Body Weight/physiology ; Bone and Bones/metabolism ; Diet, High-Fat ; Feeding Behavior/physiology ; Fructose/metabolism ; Leptin/metabolism ; Lipid Metabolism/physiology ; Liver/metabolism ; Mice ; Obesity/metabolism
Chemical Substances	Leptin ; Fructose (30237-26-4)
Language	English
Publishing date	2016-11-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	304266-2
ISSN	1432-0827 ; 0944-0747 ; 0008-0594 ; 0171-967X
ISSN (online)	1432-0827
ISSN	0944-0747 ; 0008-0594 ; 0171-967X
DOI	10.1007/s00223-016-0205-8
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