Free fall landing and interval running have different effects on trabecular bone mass and microarchitecture, serum osteocalcin, biomechanical properties, SOST expression and on osteocyte related characteristics

Author(s):  
Arnaud Boudenot ◽  
stephane PALLU ◽  
Rustem UZBEKOV ◽  
Eric DOLLEANS ◽  
Hechmi Toumi ◽  
...  

The effects of treadmill interval training (IT) and free fall exercise were evaluated on bone parameters including osteocyte related characteristics. Thirty-eight 4-month-old male Wistar rats were randomly divided into a control group (C) and exercise groups: IT, 10 free fall impacts/day with a 10s (FF10) or 20s interval between drops (FF20), 5 days/week, for 9 weeks. We assessed: BMD, microarchitecture by µCT, mechanical strength by a three-point bending test, density and occupancy of the osteocyte lacunae by toluidine blue staining, osteocalcin and NTx systemic levels by ELISA, and bone tissue Sost mRNA expression by RT-PCR. NTx levels were significantly lower in exercise groups as compared to C. In exercise groups Sost mRNA expression was significantly lower than in C. Tb.N was significantly higher for IT and FF20 compared to C; Tb.Sp was significantly lower in FF10 compared to C. Both IT and FF20 were associated with higher tibial lacunar density as compared to FF10. Compared to FF10, IT fat mass was lower, while tibial osteocyte lacunae occupancy and systemic osteocalcin level were higher. All exercise modes were efficient in reducing bone resorption. Both IT and FF impact with appropriate recovery periods might be beneficial for bone health and osteocyte related characteristics. Novelty bullets: • Interval training is beneficial for bone mineral density • Exercises decreased both bone resorption and inhibition of bone formation (sost mRNA) • Longer interval recovery time favors osteocyte lacunae density

2018 ◽  
Vol 238 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Thomas Funck-Brentano ◽  
Karin H Nilsson ◽  
Robert Brommage ◽  
Petra Henning ◽  
Ulf H Lerner ◽  
...  

WNT signaling is involved in the tumorigenesis of various cancers and regulates bone homeostasis. Palmitoleoylation of WNTs by Porcupine is required for WNT activity. Porcupine inhibitors are under development for cancer therapy. As the possible side effects of Porcupine inhibitors on bone health are unknown, we determined their effects on bone mass and strength. Twelve-week-old C57BL/6N female mice were treated by the Porcupine inhibitors LGK974 (low dose = 3 mg/kg/day; high dose = 6 mg/kg/day) or Wnt-C59 (10 mg/kg/day) or vehicle for 3 weeks. Bone parameters were assessed by serum biomarkers, dual-energy X-ray absorptiometry, µCT and histomorphometry. Bone strength was measured by the 3-point bending test. The Porcupine inhibitors were well tolerated demonstrated by normal body weight. Both doses of LGK974 and Wnt-C59 reduced total body bone mineral density compared with vehicle treatment (P < 0.001). Cortical thickness of the femur shaft (P < 0.001) and trabecular bone volume fraction in the vertebral body (P < 0.001) were reduced by treatment with LGK974 or Wnt-C59. Porcupine inhibition reduced bone strength in the tibia (P < 0.05). The cortical bone loss was the result of impaired periosteal bone formation and increased endocortical bone resorption and the trabecular bone loss was caused by reduced trabecular bone formation and increased bone resorption. Porcupine inhibitors exert deleterious effects on bone mass and strength caused by a combination of reduced bone formation and increased bone resorption. We suggest that cancer targeted therapies using Porcupine inhibitors may increase the risk of fractures.


2007 ◽  
Vol 97 (4) ◽  
pp. 776-785 ◽  
Author(s):  
Alexandre R. Lobo ◽  
Célia Colli ◽  
Eliana P. Alvares ◽  
Tullia M. C. C. Filisetti

Yacon roots have been considered a functional food due to the high levels of fructans they contains. In the present study, Ca and Mg balance, bone mass and strength, and caecum mucosal morphometry were evaluated. Growing male Wistar rats (n24) were fedad libitumcontrol diets or diets supplemented with yacon flour (5 or 7·5 % fructooligosaccharides) for 27 d. Mineral balance was evaluated in three periods of 5 d (starting on the 4th, 10th and 16th days). After the rats were killled, the bones were removed and bone mineral density was measured. Ca analyses were performed on left femurs and tibias and biomechanical testing on right femurs. The caecum was removed and tissue samples were collected for histological analysis. Caecal histology changed noticeably in rats fed yacon flour: there was an increase in the depth and number of total and bifurcated crypts as well. Yacon flour consumption significantly (P < 0·05) resulted in a positive Ca and Mg balance, leading to higher values of bone mineral retention and biomechanical properties (peak load and stiffness) when compared to the control group. The positive effects on mineral intestinal absorption, bone mass and biomechanical properties showed an important role of yacon roots in the maintenance of healthy bones. The increased number of bifurcating crypts might be related to the higher mineral absorption caused by the enlargement of the absorbing surface in the large intestine of the animals.


2018 ◽  
Vol 21 (2) ◽  
pp. 4-11 ◽  
Author(s):  
Nadezhda Y. Banshchikova ◽  
Yelena A. Letyagina ◽  
Vitaliy O. Omelchenko ◽  
Maksim A. Korolev

Background: fracture risks assessment and determination of bone mineral density are modern methods, generally accepted and widely used. However, they have limitations and disadvantages for the dynamic evaluation of bone remodeling processes in RA-patients with low BMD. The investigation of bone resorption markers is an important issue. Aims: to compare the antiresorptive activity of denosumab and alendronic acid in patients with rheumatoid arthritis and osteoporosis using β-CTX and osteocalcin (OC). Materials and methods: forty-two patients were included in the study (16 patients were treated with denosumab, 13 patients – with alendronic acid, 13 patients - control group without any osteoporosis treatment). The quantitative determination of β-CTX and OC as well as dual-energy X-ray absorptionometry (DXA) were carried out for all patients at the first visit with consecutive investigation of bone resorption markers 3 months after. The predictive capacity was determined using the ratio of observed fractures/expected fractures by FRAX. Results: The level of β-CTX 16% (median 861.6 pg/ml vs. 724.6 pg/ml, p = 0.049) and OC 39% (median 13.9 ng/ml vs 8.5 ng/ml, p = 0.047) decreased significantly in 3 month in RA patients treated with denosumab. The decrease of β-CTX (median 858.9 pg/ml vs. 821.8 pg/ml) and OC (median 14.8 ng/ml vs. 13.9 ng/ml) was observed in the group of patients treated with alendronic acid, but not reached statistical significance. Conclusions: denosumab had showed better antiresorptive activity compared with bisphosphonates, which was registered 3 month after the start of the treatment.


2016 ◽  
Vol 19 (5) ◽  
pp. 375-382
Author(s):  
Vadim V. Klimontov ◽  
Olga N. Fazullina ◽  
Alexander P. Lykov ◽  
Vladimir I. Konenkov

Aim. To determine the relationships between bone remodelling markers and bone mineral density (BMD), metabolic parameters and total body composition (TBC) in postmenopausal women with type 2 diabetes (T2D).Materials and methods. The study included 140 women who were diagnosed with T2D more than five years prior. The control group included 20 postmenopausal nondiabetic women with normal BMD. The BMD and TBC parameters were assessed by dual X-ray absorptiometry. Based on their T-scores, T2D women were divided into the following groups: normal BMD (n = 50), osteopenia (n = 50) and osteoporosis (n = 40). Serum levels of bone formation markers [osteocalcin and type 1 C-terminal collagen propeptide (CICP), osteoprotegerin (an inhibitor of bone resorption), parathyroid hormone (PHT) and urinary excretion of C-terminal telopeptides of type 1 collagen (alpha-CrossLaps, or CTX-I; a bone resorption marker)] were determined by ELISA.Results. Osteocalcin levels were decreased in all groups of T2D women (all P 0.0002), without any differences between groups. Osteoprotegerin levels were reduced in all patient groups but was significantly lower in diabetic women with osteoporosis and osteopenia compared to those with normal BMD (P = 0.003 and P = 0.01, respectively). Women with osteoporosis had higher urinary CTX-I excretion than control and diabetic women with normal BMD (P = 0.01 and P = 0.01, respectively). CICP levels did not differ between groups. PHT concentrations were increased in diabetic women (P 0.0001), without any differences between groups. After multiple regression analysis, BMI, age and CTX-I excretion were all associated with lumbar BMD (R2 = 0.38, P = 0.0007), whereas age, BMI, osteoprotegerin levels and CTX-I excretion were all predictive of BMD at the proximal femur (R2 = 0.44, P = 0.00003). There was no relationship between bone remodelling markers and HbA1c, lipid metabolism or TBC.Conclusions. In postmenopausal T2D women, osteoporosis is associated with decreased serum osteoprotegerin levels and enhanced urinary CTX-I excretion. The data do not support the existence of an interrelationship between bone remodelling markers, metabolic parameters and TBC in postmenopausal women with T2D.


2017 ◽  
Vol 42 (8) ◽  
pp. 884-892 ◽  
Author(s):  
Laura C. Ortinau ◽  
Melissa A. Linden ◽  
R. Scott Rector ◽  
Pamela S. Hinton

An often-overlooked comorbidity of type 2 diabetes (T2D) is increased fracture risk. Since traditional T2D therapies focus solely on glucose homeostasis, there is an increased need for effective treatment strategies that improve both metabolic and bone health. The current study evaluated if previously reported protective effects of exercise (EX) on cortical bone geometry and biomechanical properties are due to the prevention of obesity compared with obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats or the unique skeletal effects of exercise. Four-week-old male OLETF rats were randomly assigned to 1 of 3 groups, each fed a standard rodent chow diet until 40 weeks of age: ad libitum-fed sedentary (O-SED), ad libitum-fed EX (O-EX), or a control group body-weight−matched to the O-EX group by caloric restriction (O-CR). Ad libitum-fed sedentary Long-Evans Tokushima Otsuka (L-SED) rats were used as a lean control. EX or CR prevented the excess body mass accumulation and elevated HbA1c observed in O-SED. Total-body bone mineral density was greater in O-EX than O-CR, but similar to L-SED and O-SED. O-EX and O-CR had lower osteocalcin and TRAP5b than O-SED and L-SED. EX or CR prevented the ∼3-fold increase in CTx in O-SED versus L-SED. EX increased femoral cortical mass accumulation and expansion at the mid-diaphysis compared with O-CR. EX or CR significantly increased tissue-level stiffness and strength compared with O-SED and L-SED, but O-EX had greater whole-bone stiffness than all other groups. In summary, EX has distinct advantages over CR for improving bone biomechanical properties in hyperphagic OLETF rats.


2018 ◽  
Vol 7 (10) ◽  
pp. 297 ◽  
Author(s):  
Delia Tit ◽  
Simona Bungau ◽  
Ciprian Iovan ◽  
Delia Nistor Cseppento ◽  
Laura Endres ◽  
...  

Postmenopausal osteoporosis is the most common form of osteoporosis and one of the major public health problems in developed countries. The prevalence of this condition, associated with the physiological stage of menopause, is continuously increasing. This study evaluated the effectiveness of soy isoflavones as compared to hormone replacement therapy (HRT) in low doses, on the prevention of postmenopausal osteoporosis, by determining bone mineral density (BMD) and urinary deoxypyridinoline (D-pyr) in physiological postmenopausal women. The study was conducted over a period of 12 months, on three parallel groups, which included a total of 325 postmenopausal women (HRT group: n = 95; phytoestrogens group: n = 124; control group: n = 106). At the one-year evaluation, we observed T-score normalization in a small number of cases (5.26%, 2.42% and 0.00%, respectively). The average values of D-Pyr decreased by 11.38% in the group treated with phytoestrogens (p < 0.05) and by 15.32% in the group that followed HRT (p < 0.05); it increased by 4.38% in the control group (p > 0.05). Both therapies have beneficial effects on bone metabolism, leading to a significant decrease in the evolution of bone resorption and there are no major differences between the efficacy of HRT and phytoestrogens in terms of the effects on BMD and bone resorption.


2003 ◽  
Vol 95 (1) ◽  
pp. 300-307 ◽  
Author(s):  
T. H. Huang ◽  
S. C. Lin ◽  
F. L. Chang ◽  
S. S. Hsieh ◽  
S. H. Liu ◽  
...  

Weight bearing during exercise plays an important role in improving the mechanical properties of bone. The effect on bone of non-weight-bearing exercise such as swimming remains controversial. To investigate the effects of exercise mode on growing bone, 29 male Wistar rats (7 wk old) were randomly assigned to a running exercise group (Run, n = 9), a swimming exercise group (Swim, n = 10), or a nonexercise control group (Con, n = 10). During an 8-wk training session (20–60 min/day, 5 days/wk), the Run rats were trained at progressively increasing running speeds (12–22 m/min), and weights attached to the tail of the Swim rats were progressively increased from 0 to 2% of their body weight. The bone mineral density of the proximal tibiae of the Run rats was significantly higher than in the Swim ( P < 0.05). Femoral wet weights of the two exercise groups were significantly higher than in the control group ( P < 0.05). Interestingly, the percent difference between the tissue wet weight and dry weight (water content ratio), which is related to bone mechanical properties, was significantly higher in the tibiae of the Swim rats and the femora of both exercise groups compared with controls ( P < 0.05). Extrinsic as well as intrinsic biomechanical material properties were measured in a three-point bending test. Bone mechanical properties of the tibiae and femora of rats in the Swim and Run groups were significantly greater than those in the control group ( P < 0.05). In summary, different modes of exercise may benefit bone mechanical properties in different ways. The specific effects of swimming exercise (non-weight-bearing exercise) on bone require further study.


2010 ◽  
Vol 207 (3) ◽  
pp. 257-263 ◽  
Author(s):  
Kotaro Azuma ◽  
Stephanie C Casey ◽  
Masako Ito ◽  
Tomohiko Urano ◽  
Kuniko Horie ◽  
...  

The steroid and xenobiotic receptor (SXR) and its murine ortholog pregnane X receptor (PXR) are nuclear receptors that are expressed mainly in the liver and intestine where they function as xenobiotic sensors. In addition to its role as a xenobiotic sensor, previous studies in our laboratories and elsewhere have identified a role for SXR/PXR as a mediator of bone homeostasis. Here, we report that systemic deletion of PXR results in marked osteopenia with mechanical fragility in female mice as young as 4 months old. Bone mineral density (BMD) of PXR knockout (PXRKO) mice was significantly decreased compared with the BMD of wild-type (WT) mice. Micro-computed tomography analysis of femoral trabecular bones revealed that the three-dimensional bone volume fraction of PXRKO mice was markedly reduced compared with that of WT mice. Histomorphometrical analysis of the trabecular bones in the proximal tibia showed a remarkable reduction in bone mass in PXRKO mice. As for bone turnover of the trabecular bones, bone formation is reduced, whereas bone resorption is enhanced in PXRKO mice. Histomorphometrical analysis of femoral cortical bones revealed a larger cortical area in WT mice than that in PXRKO mice. WT mice had a thicker cortical width than PXRKO mice. Three-point bending test revealed that these morphological phenotypes actually caused mechanical fragility. Lastly, serum levels of phosphate, calcium, and alkaline phosphatase were unchanged in PXRKO mice compared with WT. Consistent with our previous results, we conclude that SXR/PXR promotes bone formation and suppresses bone resorption thus cementing a role for SXR/PXR as a key regulator of bone homeostasis.


2018 ◽  
Vol 50 (07) ◽  
pp. 562-567 ◽  
Author(s):  
Firuzan Ozer ◽  
Selcuk Dagdelen ◽  
Tomris Erbas

AbstractThe objective of this study was to investigate the effect of hyperprolactinemia and high levels of insulin-like growth factor-I (IGF-I) on bone resorption and their relation with receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in patients with prolactinoma and acromegaly. Thirty-one patients with acromegaly, 28 patients with prolactinoma, and 33 healthy individuals were included in the study. Serum concentrations of RANKL, OPG, bone alkaline phosphatase (bone ALP), osteocalcin (OC), C-terminal telopeptide of type 1 collagen (CTX), procollagen type 1 N-terminal propeptide (P1NP) and urine deoxypyridinoline (DPD) levels were detected and bone mineral density (BMD) was measured. Groups were not statistically different from each other with regard to serum levels of RANKL and OPG. The RANKL/OPG ratio was higher in the prolactinoma group than in the control group (p=0.046). A positive correlation between OPG and increasing age was detected in both the prolactinoma and control groups (r=0.524, p=0.004 and r=0.380, p=0.029, respectively). An inverse correlation was observed between IGF-I and OPG after excluding age in the prolactinoma group (r=–0.412, p=0.046). OC and bone ALP were negatively associated with RANKL in the acromegaly group (r=–0.384, p=0.036 and r=–0.528, p=0.003, respectively). There was an inverse correlation between OPG and BMD at the femoral neck in the acromegaly group (r=–0.422, p=0.02). The effect of IGF-I on bone remodeling may be partly mediated by RANKL and OPG. The RANKL/OPG ratio plays an important role in prolactinoma. A positive correlation of OPG with age and an inverse correlation with IGF-I favor the compensatory response of OPG against bone loss in the aging skeleton.


2019 ◽  
Vol 1 (2) ◽  
pp. 67
Author(s):  
Sri Widodo ◽  
Sri Kadarsih Soedjono ◽  
Denny Agustiningsih

Menopause is a permanent cessation of menstrual cycle due to reduced secretion of the hormone estrogen which can result in osteoporosis. Osteoporosis is characterized by the process of bone resorption faster than the process of bone formation, resulting in a decrease in bone mineral density and bone microarchitecture damage resulting in bones becoming brittle and easily fracturing. Physical exercise is a holistic intervention to prevent osteoporosis due to menopause. This study is a pure experimental study using a post-test only control group design research design. The subjects of the study were the 12-week-old Sprague Dawley rat. The number of groups is 5 with the number of rats per 6 animals. There was a significant difference between the ovarectomy group of rats and the ovarectomy group of mice and were given intermittent exercise treatment of CYP19 aromatase expression. Discussion: Muscle contractions that occur due to intermittent exercise treatment can produce large amounts of IL-6 and IL-6 mRNA which can stimulate estrogen production. Local estrogen production can reduce bone resorption and increase bone formation and bone density Intermittent exercise can trigger the process of the synthesis of the CYP19 aromatase enzyme in ovarectomy rat femur bones


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