The present study provides in-depth information about the effects of calcitonin on bone remodeling and will thus help in the development of future potential therapeutic strategies for postmenopausal osteoporosis. Each series of experiments was repeated at least three times. Consequently, further studies are needed to dissect the underlying mechanisms and corresponding physiological relevance during bone remodeling. Compared with saline, calcitonin treatment significantly increased the percent bone volume and trabecular number in OVX rats. Inhibition of bone resorption, which would minimize fluxes of calcium from bone into blood. PLoS ONE. Axial and appendicular bone mineral density in patients with long-term deficiency or excess of calcitonin. J Cell Physiol. J Clin Invest. N = 6 in each group. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels. Liu H, Zhang N, Liu Y, Liu L, Yin G, En L. Effect of human Wnt10b transgene overexpression on peri-implant osteogenesis in ovariectomized rats. Calcitonin, produced by cells in the thyroid gland, acts directly on osteoclasts (via receptors on the cell surface for calcitonin). Growth Hormone The present study provides further information about calcitonin at the molecular level of bone remodeling, and will thus help in future potential therapeutic studies on postmenopausal osteoporosis. Lancet Diabetes Endocrinol. Khosla S, Hofbauer LC. Salmon calcitonin inhibited osteoclastic bone resorption at concentrations of 1 pg/ml and above, while PTH and 1,25-dihydroxyvitamin D3 were without significant effect. Further investigations in this research area are necessary to comprehend the scope of Wnt effects on bone metabolism and the effectiveness of Wnt-based therapeutics on bone structure and functions. The present study used micro-CT analysis to show that calcitonin alleviated bone loss in ovariectomy-induced osteoporotic rats (Figure 1). Osteoclast-released Wnt-10b underlies cinacalcet related bone improvement in chronic kidney disease. Immunohistochemistry staining showed that the level of Wnt10b in the femur was increased in calcitonin-treated groups as compared with control groups. (2012) 7:e40272. The results obtained from a typical experiment were expressed as the means ± S.D. After blocking, the membrane was incubated with primary Ab overnight at 4°C. Endocrinol., 08 September 2020 Many studies still have a great interest in calcitonin and the effect of the bone metabolism, physiological roles, and the activities. h�b```e``Z������A��X�r,��1�����f���W�C�� �V�) ���Dk� [r3z��� �6���߭�3��Nde�;��;��O�{(f���2�������������V8�X��� ^� �;:�Z��: After chromogen properly developing the TRAP staining (AK04F-COS, COSMO BIO, Tokyo, Japan) was applied. The calcitonin-induced increase of ALP and alizarin red staining was reduced by C59 cotreatment (f in Figure 6). (A) Confocal analysis was performed in osteoclasts treated with 3 nM calcitonin alone or with C59 for 16 h. Osteoclasts were labeled with rhodamine phalloidin (red) to visualize F-actin and Nuclear Red (blue) to visualize nuclei. The volume of interest was 1.5–3.5 mm below the growth plate. increase blood calcium ion levels. In contrast to the numerous findings regarding Wnt signaling in osteoblast lineage cells, little is known about the influence of Wnt proteins on osteoclasts in the context of cell autonomy. Wnt proteins are usually involved in various aspects of bone biology, including osteoblastic, and osteoclastic functions as well as endochondral bone formation (12, 13). The osteoclasts shrink and stop bone resorption. Parathyroid hormone regulates serum calcium through its effects on bone, kidney, and the intestine:. Calcitonin treatment caused a further increase in osteocalcin and P1NP in OVX rats. Hum Gene Ther. However, C59 is a Wnt inhibitor, not specific for Wnt10b. A significant decrease in trabecular separation was found in the calcitonin treatment group. In addition, osteoblasts may also secrete Wnt10b which is interesting issue worth of more study. Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts. After decalcification, tissues were dehydrated, embedded in paraffin, and cut into 10 μm thickness per slices. By preventing the breakdown of bone, calcitonin lessens the amount of calcium in the blood. No use, distribution or reproduction is permitted which does not comply with these terms. During the observation period a significant increase in bone resorption and a significant drop in intestinal calcium absorption was observed. J Endocrinol. Figure 4. Using in vivo OVX rats and in vitro osteoclast and osteoblast cultures, we show that calcitonin induces bone formation by increasing the expression of Wnt10b in osteoclasts in ovariectomy-induced osteoporotic rats. The hormone participates in calcium (Ca ) and phosphorus metabolism. After the osteoclasts were washed with PBS, fixed with formalin substitute, and permeabilized with 0.1% Triton X-100 in PBS for 10 min, the cells were blocked in PBS containing 10% normal rabbit serum (AR1010, BOSTER, Pleasanton, CA, USA) for 1 h at room temperature. Western blot analysis was performed on osteoclasts treated with 3 nM calcitonin alone or with C59 for the various times indicated. Osteoclasts induced from bone marrow-derived monocytes were cultured on 22 × 22 mm glass coverslips in the medium described above. Calcitonin is a protein hormone that, in humans and other mammals, is mainly secreted by the parafollicular cells (C cells) of the thyroid gland. (2018) 40:134–41. The drug preparation of calcitonin is usually made from salmon calcitonin, which is more potent than human calcitonin. Immunohistochemistry labeling of Wnt10b was performed in femoral bone (Figure 3). Micro-CT analysis revealed reduced bone loss in calcitonin-treated ovariectomized rats. What stimulates PTH secretion? Dev Cell. For the ALP stain and ALP activity assay, each group was cultured for 7 days. * stimulates bone formation that is coupled to bone resorption. Articles, University of Arkansas for Medical Sciences, United States, Marqués de Valdecilla University Hospital, Spain. The calcitonin-induced inhibition of osteoclast function is believed to be due to disruption of cytoskeletal organization (distraction of actin rings) and disappearance of the cellular polarity of osteoclasts. Quantitation of these results (Figure 1B) indicated that OVX led to significant bone loss, increased trabecular separation, and decreased trabecular number compared with the control sham operation. In a culture of osteoblasts isolated from neonatal rat calvariae, the calcitonin-treated osteoclast supernatant showed an increase in mineralization, as indicated by ALP and alizarin red staining. T-HChu, J-FS, and P-JT: writing—original draft preparation. Calcitonin treatment increases the osteoclastic Wnt10b expression in metaphysis of femoral bone in ovariectomy-induced osteoporotic rats. It is well-documented that Wnt signaling plays a crucial role in many biological processes (e.g., cellular proliferation, tissue regeneration, and other systemic effects) (16). The femurs were decalcified in Decalcifying Solution (REF. Calcitonin (from thyroid gland) decreases serum Ca2+ levels by causing the calcium to go back into the bones. (2019) 20:2800. doi: 10.3390/ijms20112800, 23. Rats were anesthetized by the administration of isoflurane (Forane® AbbVie Inc., Queenborough, UK), and bilateral ovariectomy (OVX) was performed to build an osteoporosis model in OVX and OVX calcitonin-treated groups. J Bone Miner Res. Group comparisons were made by one-way ANOVA followed by the Dunnett's test using SPSS software, version 15.0 (Armonk, NY, USA). Scale bar = 50 μm. N = 6 in each group. Moreover, osteoblastic mineralization was enhanced in conditioned medium derived from calcitonin-treated osteoclasts (Figure 6). Osteoclasts also communicate to osteoblasts by clastokines (Wnt10b and S1P). The binding of calcitonin to its receptors on osteoclasts causes a series of major reactions within minutes, including loss of the ruffled border, cell retraction, and the suppression of cell motility and bone resorption (2). Lu CL, Shyu JF, Wu CC, Hung CF, Liao MT, Liu C, et al. J Bone Miner Metab. T-HChe, C-YH, J-FS, Y-NT, and T-HChu: methodology and investigation. The high bone mass attributed to increased bone formation has been found in both Calca KO and Calcr KO mice (7, 8), even though Calcr did not manifest in osteoblasts. In bone, PTH enhances the release of calcium from the large reservoir contained in the bones. Emerging role and therapeutic implication of Wnt signaling pathways in autoimmune diseases. A study indicated that Wnt signaling plays a vital role in osteoblast differentiation from both mesenchymal precursors and osteochondo progenitors as well as the proliferation and survival of osteoblasts (17). In animals, calcitonin binds to osteoclasts, preventing bone resorption. The serum of animals treated with calcitonin had decreased TRAP5b and CTX-1 but increased osteocalcin, P1NP, and Wnt10b. Uncoupling anti-resorptive, such as calcitonin, may modulate osteoblast mineralization through the controlled secretion of Wnt10b and S1P. J-FS, C-YH, T-HChe, and P-JT: study conception and design. Calcitonin indirectly increases osteoblast mineralization. The editor and reviewers' affiliations are the latest provided on their Loop research profiles and may not reflect their situation at the time of review. Protein levels were quantified by densitometry, corrected for sample loading on the basis of actin levels, and expressed as the fold change relative to the control lane. Boland GM, Perkins G, Hall DJ, Tuan RS. ��0+��˸�|W��S��^6�l��\�����~ 6Ós�0>`�b�2D,d60 1�'l� z��v���� �4b�c�@F����� �l�ᢉ�%o �� '�_� doi: 10.1002/jcb.20284, 19. Immunofluorescent labeling of Wnt10b was performed in osteoclasts isolated from rat bone marrow. %PDF-1.6 %���� 15 Briefly, cells were lysed in lysis buffer and combined with p-nitrophenyl phosphate (pNPP) as a phosphatase substrate, then incubated at room temperature for 1 h. Finally, the reaction was stopped by the addition of 0.1 M NaOH solution, and the ALP activity was estimated by the optical absorbance measured at 405 nm. On the other hand, runx2 directly induces Wnt10b expression in osteoblasts (24). This helps minimize the risk that a person will experience hypercalcemia due to the calcium produced during the breakdown of bone in the body. When the osteoclasts break down bone tissue, the calcium enters the bloodstream. No.3840, Thermo Scientific, Waltham, MA, USA) for 24 h, then transferred to 0.5 M EDTA, pH 8, for several days until a biopsy needle could be inserted in to the femur. We hypothesize that calcitonin indirectly increases osteoblastic bone formation by inducing Wnt10b expression in osteoclasts. (2018) 29:1416–27. Calcitonin functions to: stimulate osteoclast activity. Interactions. It slows bone loss and helps to increase bone density in the spine. Remember, magnesium suppresses parathyroid osteoclast production, and stimulates calcitonin which reduces osteoclast activity -- so magnesium works to keep calcium in … endstream endobj 254 0 obj <>stream Salmon calcitonin inhibited osteoclastic bone resorption at concentrations of 1 pg/ml and above, while PTH and 1,25-dihydroxyvitamin D3 were without significant effect. PTH is a bone anabolic agent and effective treatment for postmenopausal osteoporosis, maybe by its effect of increase Wnt10b production in osteoblasts (25). Thus, on the basis of the above mechanisms, calcitonin binding to CTR on osteoclasts will inhibit SPNS2 expression, causing the decreased secretion of S1P and subsequent inhibition of osteoblast activity. Thus, it is fundamentally important to uncover the mechanism by which calcitonin affects osteoblastic bone formation through its actions on osteoclasts (Figure 7). Analysis of osteoblast mineralization was performed by ALP (A) and alizarin red staining (B). Osteoclast Inhibition decreases bone resorption; Molecules that inhibit bone resorption . Cell culture assays suggest that amylin could affect bone formation and bone resorption, this latter function after its binding to the calcitonin receptor (CALCR). Decreased Wnt10b and increased TRAP expressions were found in OVX rats as compared with sham rats. Analysis of serum bone resorption markers, TRAP5b and CTX-1, revealed increased bone resorption in OVX rats compared with sham rats (Figures 2B,C). Although calcitonin has significant calcium-lowing effects in some species, it appears to have a minimal influence on blood calcium … The total protein was extracted from lysed osteoclasts treated with or without calcitonin and C59 in a lysis buffer (100 mM Tris-HCl, pH7.4, 1% NP-40) containing protease inhibitor cocktail (F1PICo25, Bio Future, New York, NY, USA). doi: 10.1152/physrev.00066.2017, 7. A decrease in serum calcium concentration and an increase in serum phosphorous concentration stimulate PTH secretion. Briefly, the study asserted that losing CTR in osteoclasts would increase the levels of sphingolipid transporter 2 (spinster 2, SPNS2), an exporter protein required for the secretion of sphingosine-1-phosphate (S1P), which can effectively induce bone formation. Currently no pharmacological formulations are available to promote bone … Figure 1. Wuster C, Raue F, Meyer C, Bergmann M, Ziegler R. Long-term excess of endogenous calcitonin in patients with medullary thyroid carcinoma does not affect bone mineral density. It is not known if Calcitonin Salmon (synthetic origin) Nasal Spray lowers the chance of having bone fractures. Osteoporosis treatment: recent developments and ongoing challenges. All authors have read and agreed to the published version of the manuscript. The sham control group comprised rats whose ovaries were exposed but not removed. Nat Commun. Introduction. Figures are representative reconstructed 3D images from each treatment group. doi: 10.1016/j.devcel.2005.03.016, 20. doi: 10.1210/en.2013-1272, 22. One function of this hormone is reducing osteoclast activity and bone … Wnt ligands have been widely studied by means of various osteoblastic models and, later, animal models. The present study provides evidence that calcitonin induces bone formation by increasing the expression of Wnt10b in osteoclasts and offers further information about the involvement of calcitonin in bone remodeling at the molecular level. Ota K, Quint P, Ruan M, Pederson L, Westendorf JJ, Khosla S, et al. After 8-week-old Sprague-Dawley (SD) rats were sacrificed, bone marrow from the tibiae and femurs were collected in 0.05% citric acid normal saline. Osteoporosis, characterized by remarkable losses of bone mineral density and strength, results in fragility fractures and subsequent high morbidity and mortality (9). The scan was performed with 180° scanning at a voltage of 80 kVp and a current of 500 μA (7.9 W output). Calcitonin increases Wnt10b and bone formation but decreases bone resorption in ovariectomized osteoporotic rats. Green arrow showed osteoclasts to secret Wnt10b; White arrow showed osteoclasts that did not secret Wnt10b. Ring artifacts and beam-hardening corrections were also performed using this software. (2013) 19:179–92. Figure 5. In other words, calcitonin enhances excretion of calcium into urine. Calcitonin acts on calcitonin receptors in bone and possibly also the kidney and gastrointestinal tract, preventing the breakdown of bone and increasing its density. TGF-beta 1-induced stimulation of 45Ca release was inhibited by calcitonin, acetazolamide, and the biphosphonate AHPrBP, three different osteoclast inhibitors. h�bbd```b``N�����"�� D귃HVN0�&߂e���B`RLv��3@$�e ɬ!6��|)�� This coupling process ensures the succession of bone formation to bone resorption in the remodeling cycle. Meanwhile, calcitonin prevents excess amounts of calcium from deteriorating bones to enter the bloodstream. *Correspondence: Pei-Jiun Tsai, pjtsai@vghtpe.gov.tw; Jia-Fwu Shyu, shyujeff@ndmctsgh.edu.tw, Front. Wnt10b has recently been recognized as a clastokine, and is potentially a therapeutic target for treating bone disorders. PTH also: * stimulates osteoclastic bone resorption indirectly to release calcium from bone. (1992) 134:141–7. Consistent with previous studies, we found that calcitonin treatment not only decreased the levels of serum bone resorption markers (i.e., TRAP5b and CTX-1) in OVX rats (Figure 2) (14, 15) but also led to increased levels of bone formation markers (i.e., osteocalcin and P1NP) in OVX rats (11, 15). e4�%�>E��Q4J�?a����kF���4�/'�i���}0�&�A�� xuz W��]�F'�{�cK���4��;=ѯ�"=��4]��}U@}]? Because calcitonin-stimulated osteoclasts could inhibit or stimulate osteoblast functions through the modulation of different cytokines, the roles that these cytokines may play in various stages of bone resorption remain unknown. Because the calcitonin receptor is only expressed in osteoclasts, the effect of calcitonin on osteoblasts maybe indirect and mediated via osteoclasts. (2013) 228:1428–32. Naot and colleagues suggested that the skeletal phenotype of an osteoclast-specific Calcr KO could enhance bone formation (6), similar to that of the global Calcr KO; thus, such findings have solved the previously mentioned contradiction. doi: 10.1172/JCI200214218, 8. Because the fluctuation in serum calcitonin levels does not have any obvious pathological outcomes, it has been suggested that calcitonin should have no physiological role in mammals. 1. Calcitonin helps with bone metabolism and calcium regulation. This hormone is also referred to as thyrocalcitonin. Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells. ���&_``��$�t�&�� �m This is a limitation in our experiment. Although calcitonin pharmacologically acts on osteoclasts to prevent bone resorption, the results of studies on genetically modified animals have shown that the physiological effect of calcitonin is in the inhibition of osteoblastic bone formation. Chambers TJ, Athanasou NA, Fuller, K. Effect of parathyroid hormone and calcitonin on the cytoplasmic spreading of isolated osteoclasts. Because Wnt10b has recently been identified as a clastokine able to increase osteoblast activity, the finding that increased Wnt10b serum levels are correlated with osteocalcin and Wnt10b expression in bone marrow in calcitonin-treated OVX rats (Figure 3) implies that Wnt10b may be involved in the effects of osteoclasts coupling to osteoblasts. These findings will help in future potential therapeutic studies of postmenopausal osteoporosis. Twenty-eight days after surgery, the following three groups (6 rats per group) were set up: (a) sham control group: rats underwent a sham operation and were subcutaneously injected with the same volume of normal saline; (b) OVX group: rats underwent the OVX operation and were subcutaneously injected with the same volume of normal saline; (c) OVX-calcitonin group: rats underwent the OVX operation and were subcutaneously injected with calcitonin (5 IU/kg/day, Miacalcic, NovartisPharma). ��ژ�RU�=���v�VÝS���vΕk�P�%܇�.��F������N������~�� �wG>���}��7��pW����B?��x�Fi��G>�� �����Z�_����%u�;v0~h�`Z��c���j>-ݧ�G'�{[ A��@�?��-9̯�bҎ)��Wo��zw�ﵧy:o��*ސ ㄓ����>K��HtP�>Ea����-����.�7n(m�Ђ5ޣ�����=�i�.5�43M�mȋc���u This molecule causes hypercalcemia by interacting with the PTH receptors, and thus increasing bone resorption, stimulating the renal reabsorption of Ca2+, and promoting the renal excretion of PO43-. When bone is broken down, the calcium contained in the bone is released into the bloodstream. It has been proposed that matrix-bound TGF-β1 could function as an effective coupling agent for actively recruiting osteoblast-lineage cells to bone-resorption positions following its osteoclast-mediated release. The serum levels of Wnt10b and bone formation and resorption markers were analyzed by ELISA. Regarding bones, calcitonin binds to calcitonin receptors on osteoclasts to inhibit bone resorption. *Indicates a significant difference (p < 0.05). In ovariectomized rats, the effects of calcitonin on the protection of bone loss and Wnt10b expression were determined by micro-CT, bone histomorphometry, and immunohistochemistry analysis. Reconstructed cross-sections were reorientated, and the region of interest (ROI) was further selected. Increases in the serum bone formation markers, osteocalcin, and P1NP, were observed in OVX rats compared with sham rats (Figures 2D,E). This suggests that the latter hormones do not increase bone resorption in intact bone through a direct effect on osteoclasts. In osteoporosis the net rate of bone resorption exceeds the rate of bone formation, resulting in a decrease in bone mass. Briefly, 18 4-month-old female Sprague–Dawley (SD) rats were purchased from a specific pathogen-free laboratory animal company (BioLASCO, Taipei, Taiwan) and separated randomly into three groups. The effect of calcitonin on bone deposition was determined in osteoporotic rats 4 weeks after ovariectomy (OVX; Figure 1). doi: 10.1016/S2213-8587(17)30188-2, 10. (2007) 101:1109–24. c7H�����Β�q F���b�����j�H�uS,!���Y�͘m`����*�����4�F��4m^plzx���k���@��LJ�� � �]�]���p|�߁�/�����H/��kH�A�R.�A�J?Pʧ(ۂE7�4S��8�f�PΡdB�ȧ�V����}��E��� Xt��� ?��3���18�_u&�-g�>�ش��(�65`��,!JU��T��,���L�0���4��y�T�*�g��V�^��!�r^��RN������y�z�~0����%B��1�ipE� ޭ�6�>���^կ����~�+k\ ����������R�8��vq�����Y�W] Though calcitonin is no longer considered an appropriate treatment option for osteoporosis, the effects of calcitonin on the coupling process between osteoclasts and osteoblasts remain uncertain. Similar finding of change of Wnt10b concentration was noted in these groups. The authors acknowledge the technical support provided by the Instrument Center of the National Defense Medical Center; micro-CT scans, bone morphometric analysis, volumetric bone mineral density, and 3D image visualization were performed by Tzu-Hung Lin and Shen-Chuan Lo, Material and Chemical Research Laboratories, Industrial Technology Research Institute. Endocrinol. By osteoclasts to release minerals including calcium from bnoe. It is believed that calcitonin does not play a prominent role in calcium homeostasis in adults, but it may be more important in skeletal development. In these cells, immunoconfocal microscopy and Western blot analysis showed that calcitonin induced an increase in Wnt10b expression. Anti-resorptive inhibit osteoclast resorption, which usually causes the inhibition of bone formation. Currently, existing murine models suggest that Wnt3a, Wnt5a, and Wnt10b are critical for osteoblast regulation, whereas Wnt14 is important for endochondral bone formation (18–20). Bones undergo constant remodeling throughout the lifetime of the organism, and this involves the continuous activity of osteoblasts and osteoclasts. As shown in Figure 2A, a significant increase in Wnt10b was found in OVX rats compared with sham rats. On the second day, after washing in 0.05% Triton X-100 PBS three times, anti-rabbit Ab conjugated FITC was applied at room temperature for 2 h. F-actin was labeled with F-Actin Labeling Kit (22663, AAT Bioquest, Sunnyvale, CA, USA), and nuclei were stained with Nuclear Red DCS1 (157199-63-8, AAT Bioquest, USA). Serum samples obtained from rats were analyzed by ELISA. The number of the osteoblast, osteoclast, and osteoclast with Wnt10b were counted. This research was supported by research grants from the Ministry of Science and Technology (MOST 108-2320-B-016-013), Ministry of National Defense-Medical Affairs Bureau (MAB-108-0088), Tri-Service General Hospital (TSGH-D109137), and Chi Mei Medical Center (CMNDMC10713) to J-FS. doi: 10.1002/jcb.21097, 21. Int J Mol Sci. Pretreatment with C59, a Wnt secretion inhibitor, further increased the calcitonin effect of Wnt10b expression within the osteoclasts and demonstrated that calcitonin increased Wnt10b release from osteoclasts. Calcitonin treatment caused a further increase in Wnt10b in OVX rats. The secretion of calcitonin, a 32 aa peptide hormone, from the parafollicular cells of the thyroid gland is induced by increased serum calcium (1) leading to rapid reduction in circulating calcium levels, mainly through the inhibition of bone resorption. h��XmO�8�+�:q�klK+���-Ҳ���q:ć��J���&���f;om�V���t��g��ZfԊpʡ� @kM��Pb5֖X# 7�0�@�0���� j$�@�\,A�QDP��b"P7�ɠ�1D�8��D:K�dZF���r��A� �Bw+�R4[��^1 *Indicates a significant difference (p < 0.05). Osteoclasts were prepared and treated as indicated in Figure 4. doi: 10.1056/NEJM198708273170904, 4. Medicines that interact with calcitonin may either decrease its effect, affect how long it … (2004) 93:1210–30. Sham-operated rats and ovariectomized (OVX) rats were treated as indicated in Figure 1. Calcitonin receptors are coupled to both cAMP-PKA- and Ca (2+)-PKC (protein kinase C)-mediated … After 4 weeks, OVX rats received a normal saline or calcitonin treatment for four additional weeks, after which the 6-month-old rats were sacrificed and underwent micro-CT analysis of the femoral bone (Figure 1). Each blot is representative of at least three replicate experiments. Although calcitonin has significant calcium-lowing effects in some species, it appears to have a minimal influence on … (1962) 193:381–2. Calcitonin reduces calcium levels in the blood by two main mechanisms: It inhibits the activity of osteoclasts, which are the cells responsible for breaking down bone. All groups were treated five times per week for 4 weeks. However, the role of Wnt ligands in skeletal physiology and disease is not fully comprehended. Recent studies of the regulatory mechanisms for the cross-talk between osteoclasts and osteoblasts have identified several bone formation-stimulating osteoclast-derived factors (i.e., clastokines) and matrix-derived growth factors, and the authors have asserted that these factors may contribute to the future design of novel osteoanabolic compounds (10). Calcitonin is a small peptide hormone secreted from the parafollicular cells of the thyroid gland in response to an increase in serum calcium.