scholarly journals Intermittent Parathyroid Hormone Administration Counteracts the Adverse Effects of Glucocorticoids on Osteoblast and Osteocyte Viability, Bone Formation, and Strength in Mice

Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2641-2649 ◽  
Author(s):  
Robert S. Weinstein ◽  
Robert L. Jilka ◽  
Maria Almeida ◽  
Paula K. Roberson ◽  
Stavros C. Manolagas
Keyword(s):  
Bone Mineral Density ◽  
Adverse Effects ◽  
Bone Formation ◽  
Bone Strength ◽  
Bone Mineral ◽  
Bone Cells ◽  
Formation Rate ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Osteocyte Apoptosis

Glucocorticoids act directly on bone cells to decrease production of osteoblasts and osteoclasts, increase osteoblast and osteocyte apoptosis, and prolong osteoclast life span. Conversely, daily injections of PTH decrease osteoblast and osteocyte apoptosis and increase bone formation and strength. Using a mouse model, we investigated whether the recently demonstrated efficacy of PTH in glucocorticoid-induced bone disease results from the ability of this therapeutic modality to counteract at least some of the direct effects of glucocorticoids on bone cells. Glucocorticoid administration to 5- to 6-month-old Swiss-Webster mice for 28 d increased the prevalence of osteoblast and osteocyte apoptosis and decreased osteoblast number, activation frequency, and bone formation rate, resulting in reduced osteoid, wall and trabecular width, bone mineral density, and bone strength. In contrast, daily injections of PTH caused a decrease in osteoblast and osteocyte apoptosis and an increase in osteoblast number, activation frequency, bone formation rate, bone mineral density, and bone strength. The decreased osteocyte apoptosis was associated with increased bone strength. When the two agents were combined, all the adverse effects of glucocorticoid excess on bone were prevented. Likewise, in cultured osteoblastic cells, PTH attenuated the adverse effects of glucocorticoids on osteoblast survival and Wnt signaling via an Akt phosphorylation-dependent mechanism. We conclude that intermittent PTH administration directly counteracts the key pathogenetic mechanisms of glucocorticoid excess on bone, thus providing a mechanistic explanation of its efficacy against glucocorticoid-induced osteoporosis.

scholarly journals Teriparatide and Abaloparatide Have a Similar Effect on Bone in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Mikkel Bo Brent ◽  
Frederik Eriksen Stoltenborg ◽  
Annemarie Brüel ◽  
Jesper Skovhus Thomsen
Keyword(s):  
Bone Mineral Density ◽  
Bone Strength ◽  
Bone Mineral ◽  
Volume Fraction ◽  
Bone Cells ◽  
Areal Bone Mineral Density ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Parathyroid Hormone Related Protein ◽  
Diaphyseal Bone

Three bone anabolic pharmaceuticals are currently approved for treatment of osteoporosis, teriparatide (PTH (1–34)), the parathyroid hormone-related protein analog abaloparatide (ABL), and romosozumab. The present study compared the effect of intermittent PTH (1–34) and ABL on bone tissue directly mole-to-mole in female mice. Forty-seven C57BL/6 mice were randomly allocated to the following groups: Baseline (n = 11), Control (Ctrl) (n = 12), PTH (n = 12), and ABL (n = 12). The mice were injected s.c. with PTH (100 µg/kg), ABL (96 µg/kg), or saline (Ctrl) five days a week for three weeks. To assess the effect of PTH and ABL, the hindlimb bones were analyzed with DXA, µCT, mechanical testing, dynamic bone histomorphometry, and histological quantification of bone cells. In addition, serum calcium concentration was determined. PTH and ABL significantly increased femoral areal bone mineral density (aBMD) (borderline significant p = 0.06 for PTH), femoral mid-diaphyseal bone strength, femoral metaphyseal and epiphyseal and vertebral bone volume fraction (BV/TV), connectivity density, volumetric bone mineral density (vBMD), and bone formation rate (BFR/BS) compared to Ctrl. In addition, ABL also significantly increased mid-diaphyseal cortical thickness and bone area compared to Ctrl. Neither PTH nor ABL significantly increased bone strength at the femoral neck. In conclusion, abaloparatide and PTH have similar bone anabolic properties when compared directly mole-to-mole in mice.

Teriparatide [rhPTH (1-34)], But Not Strontium Ranelate, Demonstrated Bone Anabolic Efficacy in Mature, Osteopenic, Ovariectomized Rats

Endocrinology ◽  
2011 ◽  
Vol 152 (5) ◽  
pp. 1767-1778 ◽  
Author(s):  
Yanfei L. Ma ◽  
Qing Q. Zeng ◽  
Leah L. Porras ◽  
Anita Harvey ◽  
Terry L. Moore ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Formation ◽  
Bone Mineral ◽  
Strontium Ranelate ◽  
Formation Rate ◽  
Ovariectomized Rats ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Ovx Rats ◽  
Dose Dependent

We compared teriparatide (TPTD) and strontium ranelate (SR) efficacy on bone formation activity in a mature rat model of estrogen-deficiency bone loss. Rats were ovariectomized (OVX) at age 6 months and permitted to lose bone for 2 months to establish osteopenia before initiation of treatment with TPTD (5 or 15 μg/kg · d sc) or SR (150 or 450 mg/kg · d oral gavage). After 3 wk, RT-PCR analyses of bone formation genes in the distal femur metaphysis showed significant elevation of collagen 1α2, osteocalcin, bone sialoprotein, alkaline phosphatase, and Runx2 gene expression at both TPTD doses, relative to OVX controls. SR had no significant effect on expression of these genes. TPTD treatment for 12 wk dose dependently increased lumbar vertebral (LV) and femoral midshaft bone mineral content (BMC) and bone mineral density over pretreatment and age-matched OVX controls. SR 150 increased BMC, and SR 450 increased BMC and bone mineral density of femoral midshaft and LV over OVX controls. There were significant dose-dependent TPTD increases of LV and femoral neck strength, and TPTD 15 also increased midshaft strength compared with pretreatment and age-matched OVX controls. SR did not enhance bone strength relative to pretreatment or age-matched OVX controls. Histomorphometry of the proximal tibial metaphysis showed dose-dependent effects of TPTD on trabecular area, number, width, and osteoblast surface, bone mineralizing surface, and bone formation rate relative to pretreatment and age-matched OVX controls, whereas SR had no effect on these parameters. These findings confirmed the bone anabolic efficacy of teriparatide, but not SR in mature, osteopenic, OVX rats.

Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength

2010 ◽  
Vol 25 (5) ◽  
pp. 948-959 ◽  
Author(s):  
Michael S Ominsky ◽  
Fay Vlasseros ◽  
Jacquelin Jolette ◽  
Susan Y Smith ◽  
Brian Stouch ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Formation ◽  
Bone Strength ◽  
Bone Mineral ◽  
Mineral Density ◽  
Cynomolgus Monkeys ◽  
Sclerostin Antibody

scholarly journals Teriparatide Increases Bone Formation and Bone Mineral Density in Adult Women With Anorexia Nervosa

2014 ◽  
Vol 99 (4) ◽  
pp. 1322-1329 ◽  
Author(s):  
Pouneh K. Fazeli ◽  
Irene S. Wang ◽  
Karen K. Miller ◽  
David B. Herzog ◽  
Madhusmita Misra ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Anorexia Nervosa ◽  
Bone Formation ◽  
Bone Mineral ◽  
Adult Women ◽  
Mineral Density

Influence of electro-acupuncture on bone mineral density, bone strength and ultrastructure in ovariectomized rats

Bone ◽  
2006 ◽  
Vol 38 (3) ◽  
pp. 27-28 ◽  
Author(s):  
Z.G. Luo ◽  
A.T. Wang ◽  
W.S. Yu ◽  
Y. Zhao ◽  
P. Hu ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Strength ◽  
Bone Mineral ◽  
Ovariectomized Rats ◽  
Mineral Density

475 A Novel Means of Assessing Bone Mineral Density and Bone Strength in Patients With Inflammatory Bowel Disease Undergoing CT Enterography

2013 ◽  
Vol 144 (5) ◽  
pp. S-86
Author(s):  
Nicholas K. Weber ◽  
Jeff L. Fidler ◽  
Bart L. Clarke ◽  
Sundeep Khosla ◽  
Joel G. Fletcher ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Inflammatory Bowel Disease ◽  
Bone Strength ◽  
Bone Mineral ◽  
Bowel Disease ◽  
Ct Enterography ◽  
Mineral Density ◽  
Inflammatory Bowel

scholarly journals Evaluation of bone mineral density (BMD) and indicators of bone turnover in patients with hemophilia

2018 ◽  
Vol 18 (2) ◽  
pp. 206-210 ◽  
Author(s):  
Mehmet Dagli ◽  
Ali Kutlucan ◽  
Sedat Abusoglu ◽  
Abdulkadir Basturk ◽  
Mehmet Sozen ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Vitamin D ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Mineral ◽  
Type I ◽  
Healthy Controls ◽  
Mineral Density ◽  
Lymphocyte Ratio ◽  
Significant Difference

A decrease in bone mass is observed in hemophilic patients. The aim of this study was to evaluate bone mineral density (BMD), parathyroid hormone (PTH), 25-hydroxy vitamin D (vitamin D), and a bone formation and resorption marker, procollagen type I N-terminal propeptide (PINP) and urinary N-terminal telopeptide (uNTX) respectively, in hemophilic patients and healthy controls. Laboratory parameters related to the pathogenesis of bone loss such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were also evaluated. Thirty-five men over 18 years of age, with severe hemophilia (A and B) and receiving secondary prophylaxis, were included in the study. The same number of age-, sex-, and ethnicity-matched healthy controls were evaluated. Anthropometric, biochemical, and hormonal parameters were determined in both groups. No significant difference in anthropometric parameters was found between the two groups. The BMD was low in 34% of hemophilic patients. Vitamin D, calcium, and free testosterone levels were significantly lower (p < 0.001, p = 0.011, p < 0.001, respectively), while PTH, PINP, and activated partial thromboplastin time (aPTT) levels were significantly higher (p < 0.014, p = 0.043, p < 0.001, respectively), in hemophilic patients compared to controls. There was no significant difference between the two groups in NLR, PLR, phosphorus, thyroid-stimulating hormone, and uNTX level. The reduction of bone mass in hemophilic patients may be evaluated using the markers of bone formation and resorption, enabling early detection and timely treatment.

scholarly journals Beyond Bone Mineral Density: A New Dual X-Ray Absorptiometry Index of Bone Strength to Predict Fragility Fractures, the Bone Strain Index

2021 ◽  
Vol 7 ◽  
Author(s):  
Fabio Massimo Ulivieri ◽  
Luca Rinaudo
Keyword(s):  
Bone Mineral Density ◽  
Density Distribution ◽  
Bone Strength ◽  
Bone Quality ◽  
Bone Mineral ◽  
Fragility Fracture ◽  
Bone Strain ◽  
Mineral Density ◽  
Strain Index ◽  
X Ray

For a proper assessment of osteoporotic fragility fracture prediction, all aspects regarding bone mineral density, bone texture, geometry and information about strength are necessary, particularly in endocrinological and rheumatological diseases, where bone quality impairment is relevant. Data regarding bone quantity (density) and, partially, bone quality (structure and geometry) are obtained by the gold standard method of dual X-ray absorptiometry (DXA). Data about bone strength are not yet readily available. To evaluate bone resistance to strain, a new DXA-derived index based on the Finite Element Analysis (FEA) of a greyscale of density distribution measured on spine and femoral scan, namely Bone Strain Index (BSI), has recently been developed. Bone Strain Index includes local information on density distribution, bone geometry and loadings and it differs from bone mineral density (BMD) and other variables of bone quality like trabecular bone score (TBS), which are all based on the quantification of bone mass and distribution averaged over the scanned region. This state of the art review illustrates the methodology of BSI calculation, the findings of its in reproducibility and the preliminary data about its capability to predict fragility fracture and to monitor the follow up of the pharmacological treatment for osteoporosis.

IGF-binding protein-5 stimulates osteoblast activity and bone accretion in ovariectomized mice

2001 ◽  
Vol 281 (2) ◽  
pp. E283-E288 ◽  
Author(s):  
Dennis L. Andress
Keyword(s):  
Bone Formation ◽  
Binding Protein ◽  
Formation Rate ◽  
Bone Matrix ◽  
Secretory Protein ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Ovariectomized Mice ◽  
Osteoblast Activity

Insulin-like growth factor binding protein-5 (IGFBP-5) is an osteoblast secretory protein that becomes incorporated into the mineralized bone matrix. In osteoblast cultures, IGFBP-5 stimulates cell proliferation by an IGF-independent mechanism. To evaluate whether IGFBP-5 can stimulate osteoblast activity and enhance bone accretion in a mouse model of osteoblast insufficiency, daily subcutaneous injections of either intact [IGFBP-5 (intact)] or carboxy-truncated IGFBP-5 [IGFBP-5-(1–169)] were given to ovariectomized (OVX) mice for 8 wk. Femur and spine bone mineral density (BMD), measured every 2 wk, showed early and sustained increases in response to IGFBP-5. Bone histomorphometry of cancellous bone showed significant elevations in the bone formation rate in both the femur metaphysis [IGFBP-5- (1)] only) and spine compared with OVX controls. IGFBP-5 also stimulated osteoblast number in the femur IGFBP-5-(1–169) only) and spine. These data indicate that IGFBP-5 effectively enhances bone formation and bone accretion in OVX mice by stimulating osteoblast activity. The finding that IGFBP-5-(1–169) is bioactive in vivo indicates that the carboxy-terminal portion is not required for this bone anabolic effect.

scholarly journals Bone Mineral Density Accrual Determines Energy Expenditure with Refeeding in Anorexia Nervosa and Supersedes Return of Menses

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Melissa Sum ◽  
Laurel Mayer ◽  
Michelle P. Warren
Keyword(s):  
Bone Mineral Density ◽  
Anorexia Nervosa ◽  
Weight Gain ◽  
Energy Expenditure ◽  
Bone Formation ◽  
Bone Mineral ◽  
Subgroup Analysis ◽  
Resting Energy Expenditure ◽  
Nutritional Rehabilitation ◽  
Mineral Density

Osteopenia and osteoporosis are major complications of anorexia nervosa (AN). Since bone is a tissue requiring large amounts of energy, we examined the disproportionate increase in resting energy expenditure (REE) that occurs with refeeding of AN patients to determine if it was related to bone accretion. Thirty-seven AN patients aged23.4±4.8years underwent a behavioral weight-gain protocol lasting a median of 66 days; 27 remained amenorrheic, and 10 regained menses. Sixteen controls aged25.1±4.7years were age- and % IBW matched with patients. REE was measured using a respiratory chamber-indirect calorimeter. Significant correlations were found between REE and changes in spine (r=0.48,P<0.02) and leg (r=0.43,P<0.05) BMDs in AN patients. Further subgroup analysis of the amenorrheics revealed significant correlation between REE and change in spine BMD (r=0.59,P<0.02) and higher IGF-1 after weight gain compared to controls. Amenorrheics also had lower BMDs. These findings were absent in the regained menses group. The increase in REE seen in women with AN during nutritional rehabilitation may be related to active bone formation, which is not as prominent when menses have returned.

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