Teriparatide and Abaloparatide Have a Similar Effect on Bone in Mice

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.

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

Endocrinology ◽

10.1210/en.2009-1488 ◽

2010 ◽

Vol 151 (6) ◽

pp. 2641-2649 ◽

Cited By ~ 88

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.

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Fracture risk among men, in relation to osteopenia and osteoporosis defined by areal bone mineral density

Bone Abstracts ◽

10.1530/boneabs.1.pp343 ◽

2013 ◽

Author(s):

Julie Pasco ◽

Stephen Lane ◽

Sharon Brennan ◽

Elizabeth Timney ◽

Gosia Bucki-Smith ◽

...

Keyword(s):

Bone Mineral Density ◽

Fracture Risk ◽

Bone Mineral ◽

Areal Bone Mineral Density ◽

Mineral Density

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Evaluation of vertebral volumetric vs. areal bone mineral density during growth

Bone ◽

10.1016/s8756-3282(97)00057-4 ◽

1997 ◽

Vol 20 (6) ◽

pp. 553-556 ◽

Cited By ~ 22

Author(s):

S.M. Ott ◽

M. O'Hanlan ◽

E.W. Lipkin ◽

L. Newell-Morris

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Areal Bone Mineral Density ◽

Mineral Density

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

Bone ◽

10.1016/j.bone.2006.01.116 ◽

2006 ◽

Vol 38 (3) ◽

pp. 27-28 ◽

Cited By ~ 1

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

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Relationship of age to bone microstructure independent of areal bone mineral density

Journal of Bone and Mineral Research ◽

10.1002/jbmr.1468 ◽

2012 ◽

Vol 27 (3) ◽

pp. 637-644 ◽

Cited By ~ 83

Author(s):

Kristy M Nicks ◽

Shreyasee Amin ◽

Elizabeth J Atkinson ◽

B Lawrence Riggs ◽

L Joseph Melton ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Bone Microstructure ◽

Areal Bone Mineral Density ◽

Mineral Density ◽

Relationship Of

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

Gastroenterology ◽

10.1016/s0016-5085(13)60319-4 ◽

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

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

Frontiers in Medicine ◽

10.3389/fmed.2020.590139 ◽

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.

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