SUN-335 Abaloparatide Prevents Unloading-Induced Bone Loss in Adult Rats

Abstract Disuse osteoporosis (bone loss resulted from a reduction in mechanical loading) occurs in patients due to prolonged bed rest, paralysis and application of braces. Abaloparatide (ABL) is a synthetic peptide analog of PTHrP that has been shown to promote bone formation with limited bone resorption. ABL was approved by the FDA in 2017 to treat osteoporosis in postmenopausal women at high fracture risk. Yet, the ability of ABL to prevent bone loss in disuse is unknown. We hypothesized that ABL would prevent bone loss in the hindlimb unloading (HLU) rat model of disuse osteoporosis. Adult male Wistar rats, 13–14 weeks of age, were assigned to 1 of 4 groups (10 rats/group): ambulatory + vehicle (CON-VEH), ambulatory + ABL (CON-ABL), HLU + vehicle (HLU-VEH) or HLU + ABL (HLU-ABL). The rats received a daily subcutaneous injection of ABL (25µg/kg/day) or vehicle for 28 days. Blood serum was collected on day 0, 7, 14 and 28 to examine the expression of bone markers such as osteocalcin (OCN) and TRAcP5b. pQCT scans were acquired at the proximal tibia at day 0 and 28 to measure changes in the total and trabecular vBMD. Following euthanasia, trabecular (Tb) and cortical (Ct) bone microarchitecture from femurs, tibias and L4 vertebrae were assessed using µCT. Femurs were mechanically tested to failure in 3-point bending to determine ultimate load (N) and stiffness (N/mm). Treatment effects were evaluated using 2-way ANOVA. Effects were considered significant at p < 0.05. Data reported as mean±SD. HLU led to loss of bone density and structure that were prevented by ABL. Longitudinal pQCT revealed significant increases in total vBMD in ABL-CON (52±17%) vs. VEH-CON (20±5%); and in HLU-ABL (24±6%) vs. HLU-VEH (-2±3%) (p<0.001 for both). Significant differences were observed in the µCT analysis of the distal femur: Tb.BV/TV, thickness and BMD were 43.7%, 12.9% and 27.4% lower, respectively, in HLU-VEH compared to CON-VEH (p<0.05 for all). ABL prevented these negative effects, such that Tb.BV/TV, thickness and BMD were 66.5%, 39% and 50.3% higher in HLU-ABL compared to HLU-VEH (p<0.01 for all). A positive impact of ABL on bone morphology was also seen in the CON-VEH rats. CON-ABL had greater femoral stiffness (+22.9%, p=0.03) and ultimate load (+20.5%, p=0.01) than CON-VEH. Vertebral and tibial trabecular parameters mimicked the distal femur parameters. Serum TRAcP5b did not differ among groups, yet both ABL groups had higher OCN levels than the VEH-treated control groups (+63%, p<0.05). We demonstrated positive effects of ABL on BMD, trabecular bone mass and structure in both ambulating and unloaded rats. These results are consistent with prior studies showing positive effects of ABL on bone mass, structure and strength in OVX and ORX rats. Limits include only male rats and 1 dose of ABL. However, the results observed in this study provide a strong rationale for investigating the ability of ABL to prevent disuse bone loss in humans.

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Magnesium Picolinate Improves Bone Formation by Regulation of RANK/RANKL/OPG and BMP-2/Runx2 Signaling Pathways in High-Fat Fed Rats

Nutrients ◽

10.3390/nu13103353 ◽

2021 ◽

Vol 13 (10) ◽

pp. 3353

Author(s):

Emre Sahin ◽

Cemal Orhan ◽

Tansel Ansal Balci ◽

Fusun Erten ◽

Kazim Sahin

Keyword(s):

Bone Loss ◽

Bone Formation ◽

High Fat Diet ◽

Male Rats ◽

High Fat ◽

Mineral Density ◽

Protein Levels ◽

Prevent Bone Loss ◽

Osteogenic Protein ◽

Affect Bone Metabolism

Magnesium (Mg) deficiency may affect bone metabolism by increasing osteoclasts, decreasing osteoblasts, promoting inflammation/oxidative stress, and result in subsequent bone loss. The objective of the present study was to identify the molecular mechanism underlying the bone protective effect of different forms of Mg (inorganic magnesium oxide (MgO) versus organic magnesium picolinate (MgPic) compound) in rats fed with a high-fat diet (HFD). Forty-two Wistar albino male rats were divided into six group (n = 7): (i) control, (ii) MgO, (iii) MgPic, (iv) HFD, (v) HFD + MgO, and (vi) HFD + MgPic. Bone mineral density (BMD) increased in the Mg supplemented groups, especially MgPic, as compared with the HFD group (p < 0.001). As compared with the HFD + MgO group, the HFD + MgPic group had higher bone P (p < 0.05) and Mg levels (p < 0.001). In addition, as compared to MgO, MgPic improved bone formation by increasing the levels of osteogenetic proteins (COL1A1 (p < 0.001), BMP2 (p < 0.001), Runx2 (p < 0.001), OPG (p < 0.05), and OCN (p < 0.001), IGF-1 (p < 0.001)), while prevented bone resorption by reducing the levels of RANK and RANKL (p < 0.001). In conclusion, the present data showed that the MgPic could increase osteogenic protein levels in bone more effectively than MgO, prevent bone loss, and contribute to bone formation in HFD rats.

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A Review on Current Osteoporosis Research: With Special Focus on Disuse Bone Loss

Journal of Osteoporosis ◽

10.4061/2011/293808 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 38

Author(s):

Roy Yuen-chi Lau ◽

Xia Guo

Keyword(s):

Bone Loss ◽

Bone Mass ◽

Muscular Contraction ◽

Special Focus ◽

Primary Osteoporosis ◽

Disuse Osteoporosis ◽

Space Flights ◽

Increased Risk ◽

Osteoporosis Research ◽

Effective Treatments

Osteoporosis is a multifactorial skeletal disorder characterized by decreased bone mass and deteriorated microarchitecture that lead to increased risk of fracture. The disuse osteoporosis refers to bone mass decrements under conditions of decreased mechanical loading, including decreased ground force reaction, muscular contraction, and microgravity-related bone loss in astronauts after space flights. Although there are many effective treatments available for primary osteoporosis, there is a lack of effective treatments for disuse osteoporosis. This is because that the aetiology, pathophysiology, and resultant pathology of disuse osteoporosis differ from those of primary osteoporosis. The objective of this paper is to examine the unique pathology and underlying pathophysiology of disuse osteoporosis.

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Total Flavonoids of Drynariae Rhizoma Prevent Bone Loss Induced by Hindlimb Unloading in Rats

Molecules ◽

10.3390/molecules22071033 ◽

2017 ◽

Vol 22 (7) ◽

pp. 1033 ◽

Cited By ~ 7

Author(s):

Shuanghong Song ◽

Ziyang Gao ◽

Xujun Lei ◽

Yinbo Niu ◽

Yuan Zhang ◽

...

Keyword(s):

Bone Loss ◽

Hindlimb Unloading ◽

Total Flavonoids ◽

Prevent Bone Loss

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Space-related bone mineral redistribution and lack of bone mass recovery after reambulation in young rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.274.2.r324 ◽

1998 ◽

Vol 274 (2) ◽

pp. R324-R334 ◽

Cited By ~ 18

Author(s):

Marie-Hélène Lafage-Proust ◽

Philippe Collet ◽

Jean Michel Dubost ◽

Norbert Laroche ◽

Christian Alexandre ◽

...

Keyword(s):

Bone Loss ◽

Bone Mineral ◽

Distal Femur ◽

Bone Volume ◽

Male Rats ◽

Long Bones ◽

Active Recovery ◽

X Ray ◽

Bone Calcium ◽

Calcium And Phosphorus

This study reports the effects of a 14-day spaceflight followed by a 14-day reambulation period on bones of 56-day-old male rats compared with synchronous (S) and vivarium (V) control animals. Femur, tibia, and humerus bone mineral densities (BMD); bone calcium and phosphorus concentrations ([Ca2+] and [P]), measured by X-ray microanalysis (XRM), on tibia, vertebra, and calvaria; and histomorphometric data on proximal primary and secondary spongiosae (I and II SP, respectively) of the tibia and humerus were measured. After the flight in flown rats (compared with S), BMD was lower in the distal femur and remained similar to S in humerus and tibia, [Ca2+] and [P] were lower in tibia II SP and higher in calvaria, tibia I SP width and II SP bone volume were lower, resorption was markedly higher in tibia II SP, and no difference in formation parameters was observed. After reambulation, BMD was lower in long bones of both flight and S groups compared with V. Bone loss appeared in humeral II SP and worsened in tibial II SP in flown rats. Tibial formation parameters were higher in flown rats compared with V and S, indicating the onset of an active recovery. Tibial XRM [Ca2+] and [P] in flown rats remained below control levels.

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The Effects of Technology Supports on Community Grocery Shopping Skills for Students With Intellectual and Developmental Disabilities: A Meta-Analysis

Journal of Special Education Technology ◽

10.1177/0162643421989970 ◽

2021 ◽

pp. 016264342198997

Author(s):

Sojung Jung ◽

Ciara Ousley ◽

David McNaughton ◽

Pamela Wolfe

Keyword(s):

Developmental Disabilities ◽

Positive Impact ◽

Single Case ◽

Effect Sizes ◽

Future Research ◽

Intellectual And Developmental Disabilities ◽

Positive Effects ◽

Analytic Review ◽

Wide Range ◽

The Impact

In this meta-analytic review, we investigated the effects of technology supports on the acquisition of shopping skills for students with intellectual and developmental disabilities (IDD) between the ages of 5 and 24. Nineteen single-case experimental research studies, presented in 15 research articles, met the current study’s inclusion criteria and the What Works Clearinghouse (WWC) standards. An analysis of potential moderators was conducted, and we calculated effect sizes using Tau-U to examine the impact of age, diagnosis, and type of technology on the reported outcomes for the 56 participants. The results from the included studies provide evidence that a wide range of technology interventions had a positive impact on shopping performance. These positive effects were seen for individuals across a wide range of ages and disability types, and for a wide variety of shopping skills. The strongest effect sizes were observed for technologies that provided visual supports rather than just auditory support. We provide an interpretation of the findings, implications of the results, and recommended areas for future research.

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Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen deficiency-induced bone loss

iScience ◽

10.1016/j.isci.2021.102224 ◽

2021 ◽

pp. 102224

Author(s):

Juliane Lehmann ◽

Sylvia Thiele ◽

Ulrike Baschant ◽

Tilman D. Rachner ◽

Christof Niehrs ◽

...

Keyword(s):

T Cells ◽

Bone Loss ◽

Bone Mass ◽

Estrogen Deficiency ◽

High Bone Mass ◽

High Bone

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The Influence of Dynamic and Adaptive Marketing Capabilities on the Performance of Portuguese SMEs in the B2B International Market

Sustainability ◽

10.3390/su13020579 ◽

2021 ◽

Vol 13 (2) ◽

pp. 579

Author(s):

Caroline Reimann ◽

Fernando Carvalho ◽

Marcelo Duarte

Keyword(s):

Positive Impact ◽

International Marketing ◽

International Market ◽

Marketing Capabilities ◽

Moderating Effects ◽

Competitive Intensity ◽

Positive Effects ◽

Marketing Performance ◽

Market Learning ◽

Positive Effect

The present investigation aims study the sustainability of the business model of the Portuguese SMEs operating in the B2B International market analyzing the influence of dynamic marketing capabilities and adaptive marketing capabilities in their international marketing performance. It will also analyze the moderating effects of Competitive Intensity within this international scenario. A quantitative study was developed, using a questionnaire as a research method. In total, 335 valid responses were collected from Portuguese SMEs in June 2020. To test the hypotheses, multiple hierarchical regressions were performed. As for the analyzes involving Competitive Intensity environments, namely low and high intensity, dummies were developed to evaluate the different effects produced by the capacities in the International Marketing Performance. This study shows the positive impact of the dynamic marketing capabilities and adaptive marketing capabilities on the international marketing performance of the surveyed companies, essentially from the product development management, supply chain management, vigilant market learning and open marketing. when in a low competitive intensity environment only dynamic marketing capabilities had a positive effect on performance, but in a high, competitive, intensity environment both dynamic marketing capabilities and adaptive marketing capabilities showed positive effects in relation to performance. This study innovates by bringing international marketing, through two marketing capacities, from the perspective of SMEs that perform B2B activities.

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Paleolithic Diet—Effect on the Health Status and Performance of Athletes?

Nutrients ◽

10.3390/nu13031019 ◽

2021 ◽

Vol 13 (3) ◽

pp. 1019

Author(s):

Barbara Frączek ◽

Aleksandra Pięta ◽

Adrian Burda ◽

Paulina Mazur-Kurach ◽

Florentyna Tyrała

Keyword(s):

Blood Pressure ◽

Body Mass ◽

Positive Impact ◽

Model Assessment ◽

Paleolithic Diet ◽

Short Term ◽

Positive Effects ◽

Short And Long Term ◽

The Impact

The aim of this meta-analysis was to review the impact of a Paleolithic diet (PD) on selected health indicators (body composition, lipid profile, blood pressure, and carbohydrate metabolism) in the short and long term of nutrition intervention in healthy and unhealthy adults. A systematic review of randomized controlled trials of 21 full-text original human studies was conducted. Both the PD and a variety of healthy diets (control diets (CDs)) caused reduction in anthropometric parameters, both in the short and long term. For many indicators, such as weight (body mass (BM)), body mass index (BMI), and waist circumference (WC), impact was stronger and especially found in the short term. All diets caused a decrease in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), albeit the impact of PD was stronger. Among long-term studies, only PD cased a decline in TC and LDL-C. Impact on blood pressure was observed mainly in the short term. PD caused a decrease in fasting plasma (fP) glucose, fP insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) and glycated hemoglobin (HbA1c) in the short run, contrary to CD. In the long term, only PD caused a decrease in fP glucose and fP insulin. Lower positive impact of PD on performance was observed in the group without exercise. Positive effects of the PD on health and the lack of experiments among professional athletes require longer-term interventions to determine the effect of the Paleo diet on athletic performance.

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