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Teriparatide

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Osteoporotic Fracture and Systemic Skeletal Disorders

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Abstract

Intermittently administered parathyroid hormone (PTH) promotes bone formation in both human and animal studies. By varying the duration of exposure, PTH can modulate genes leading to increased bone formation. The osteogenic mechanisms involved include the stimulation of osteoprogenitor cells, osteoblasts, and osteocytes, leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signaling, increased stem-cell mobilization, and mediation of the RANKL/OPG pathway. Daily administration of human recombinant PTH(1-34) (teriparatide) increases activation frequency, and modeling and remodeling-based bone formation. In postmenopausal women, daily teriparatide increases bone mineral density and decreases vertebral fractures by 65%, and non-vertebral fragility fractures by 53% compared with placebo. Evidence from an individual patient-level data meta-analysis, which included 8644 patients, revealed a reduction of 56% in hip fractures compared with controls. Teriparatide decreased the risk of new vertebral and clinical fractures by 56% and 52%, respectively, compared to risedronate in women with severe osteoporosis. Treatment with teriparatide is associated with minor adverse effects, including hypercalcemia, nausea, dizziness, headache, leg cramps, and arthralgia. Candidates for teriparatide treatment are women and men at high risk of future osteoporosis-related fractures, including those with recent, severe, or multiple vertebral fractures, and other osteoporosis-related fractures with low bone mineral density.

The present invited review was completed and submitted to the publisher on 19-Nov-19. 

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Abbreviations

aBMD:

Areal bone mineral density

AR:

Anti-resorptives

b-ALP:

Bone-specific alkaline phosphatase

BMD:

Bone mineral density

BMPs:

Bone morphogenic proteins

BMUs:

Bone multicellular units

cAMP:

Cyclic-adenosine monophosphate

CTX-I:

C-terminal cross-linking telopeptide of type I collagen

DNA:

Deoxyribonucleic acid

DXA:

Dual-energy X-ray absorptiometry

EuroFORS:

European Forsteo Study

FEA:

Finite elements analysis

FPT:

Fracture Prevention Trial

FTIRI:

Fourier transform infrared imaging

hPTH:

Human parathyroid hormone

HR-QCT:

High resolution quantitative computerized tomography

IGF-1:

Insulin-like growth factor type 1

IGF-2:

Insulin-like growth factor type 2

MS/BS%:

Mineralizing surface %

PICP:

Procollagen type I carboxy-terminal propeptide

PINP:

Procollagen type I amino-terminal propeptide

PKA:

Protein kinase A

PKC:

Protein kinase C

PTH:

Parathyroid hormone

PTH1R:

PTH/PTH-related peptide receptor

QCT:

Quantitative computerized tomography

RANKL:

Receptor activator of nuclear factor kappa-Β ligand

RUNX2:

Runt-related transcription factor 2

TNF-ß:

Tumor necrosis factor-ß

vBMD:

Volumetric bone mineral density

VERO:

Vertebral fracture treatment comparisons in osteoporotic women

μCT:

Microcomputed tomography

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Acknowledgments

We are grateful to Dr. Venkatesh (Gary) Krishnan, Lilly Research Laboratories, for his critical review of the chapter.

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Authors and Affiliations

  1. Lilly Research Laboratories, Windlesham, UK

    Fernando Marin

  2. Lilly Research Laboratories, Indianapolis, IN, USA

    Yanfei L. Ma

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  1. Fernando Marin
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  2. Yanfei L. Ma
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Editors and Affiliations

  1. Niigata Bone Science Institute, Niigata Rehabilitation Hospital, Niigata, Japan

    Hideaki E. Takahashi

  2. Department of Anatomy, Cell Biology and Physiology, Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN, USA

    David B. Burr

  3. Niigata Bone Science Institute, Niigata Rehabilitation Hospital, Niigata, Japan

    Noriaki Yamamoto

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Marin, F., Ma, Y.L. (2022). Teriparatide. In: Takahashi, H.E., Burr, D.B., Yamamoto, N. (eds) Osteoporotic Fracture and Systemic Skeletal Disorders. Springer, Singapore. https://doi.org/10.1007/978-981-16-5613-2_22

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  • DOI: https://doi.org/10.1007/978-981-16-5613-2_22

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