Biophysics and the nonlinear dynamics instigated by a special hormone Sana Javed a, b, * , Ayesha Sohail b , Anila Asif c , Alessandro Nutini d a Department of Biochemistry and Biophysics, Stockholm University, Science for Life Laboratory, Box 1031,17121, Solna, Sweden b Department of Mathematics, Comsats University Islamabad, Lahore, 54000, Pakistan c Interdisciplinary Science, Comsats University Islamabad, Lahore, 54000, Pakistan d Center for Study in Motor Science, 94 via di Tiglio, loc. Arancio, 55100, Lucca, Italy article info Article history: Received 22 March 2019 Received in revised form 8 May 2019 Accepted 16 May 2019 Available online xxx Keywords: Calcitonin Bone remodeling Osteoporosis Mathematical modeling Multiscale analysis abstract Calcitonin, a potent hypocalcemic hormone, plays a vital role in inhibiting osteoclastic activities and suppressing bone removal. The physiological characteristics of calcitonin have long been discussed, along a few recommending calcitonin as a vestigial hormone. The basis for this article is to discuss the role of low and high levels of calcitonin in normal and osteoprotic bone turnover. The effect of calcitonin on the receptor activator of nuclear factor kappa-ligand and osteoclasts has been demonstrated using numerical simulations. This behavior recommends that treatment of osteoporosis via calcitonin does not provide the required upshots. For effectiveness calcitonin must be advised along with a combined therapy like aspirin which agrees with the experimental results available in the literature. © 2019 Elsevier Ltd. All rights reserved. 1. Introduction The bone remodeling process, interfaced with mathematical modeling provides a deep analysis to understand the role of key factors involved in making a skeletal system mature and perpetuate (Sohail et al., 2019). In bone remodeling, osteoclasts and osteoblasts play vital roles (Javed et al., 2018, 2019). Osteoclasts are lethally differentiated myeloid multinucleated cells that are exclusively transformed to eradicate mineralized bone milieu. Precursors of osteoclasts flow in the blood and bone marrow and adult osteo- clasts are produced from synthesis of the precursors. Such evolu- tion takes place after the signaling through receptor activators of NF-kb and its ligand. During bone resorption, osteoclasts append to the bone and develop tight seals with the underlying bone matrix in roughly circular extensions of their cytoplasm, and within these sealed zones they form ruffled border membranes. By this sealing and secretory means, the bone matrix is concurrently degraded and bone minerals are dissolved, while protecting neighboring cells from the harmful effects of HCl. Osteoblasts are mono nucleated cellular units derived from mesenchymal stem cells. They are responsible for manufacturing of the major proteins of bone as well as type 1 collagen like osteocalcin and osteopontin, which compile the organic milieu of bone. These cells are also accountable for the mineralization of bone and fabricate enzyme alkaline phosphates. Recent investigations exhibit the role of osteoblasts as an impera- tive component in governing osteoclastogenesis. The tight coupling between osteoclasts and osteoblasts is mainly regulated by a signaling pathway recognized as OPG/RANK/RANKL pathway. (see Tables 1 and 2). Osteoprotegerin (OPG), a soluble decoy receptor, functions as a bone defender and inhibits osteoclastogenesis through hindrance of osteoclasts. Receptor activator of nuclear factor kappa beta (NF- kb), abbreviated as RANK, is accountable for differentiation, per- formance and endurance of osteoclasts and plays a key role in bone resorption. It enhances the osteoclastogenesis. RANK is expressed on the surface of osteoclasts precursors. OPG and RANK both re- ceptors show affinity to the same ligand RANKL but have contra- dictory effects on osteoclastogenesis. Formation of OPG-RANKL complex jams the process of bone resorption which consequently restrains the osteoclastogenesis while formation of RANK-RANKL complex initiates the functioning of osteoclasts and increase bone resorption. RANKL is the only cytokine which plays a vital part in bone metabolism. Several experiments performed on RANK- * Corresponding author. Department of Biochemistry and Biophysics, Stockholm University, Science for Life Laboratory, Box 1031, 17121, Solna, Sweden. E-mail address: sana.javed@scilifelab.se (S. Javed). Contents lists available at ScienceDirect Progress in Biophysics and Molecular Biology journal homepage: www.elsevier.com/locate/pbiomolbio https://doi.org/10.1016/j.pbiomolbio.2019.05.005 0079-6107/© 2019 Elsevier Ltd. All rights reserved. Progress in Biophysics and Molecular Biology xxx (xxxx) xxx Please cite this article as: Javed, S et al., Biophysics and the nonlinear dynamics instigated by a special hormone, Progress in Biophysics and Molecular Biology, https://doi.org/10.1016/j.pbiomolbio.2019.05.005