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Calcitonin Therapy in Osteoporosis

  • Review Article
  • Published:
Treatments in Endocrinology

Abstract

Osteoporosis is the most prevalent metabolic bone disease and is characterized by diminished bone strength predisposing to an increased risk of fracture. Its incidence is particularly high in postmenopausal women but it can also affect other groups, such as men and patients receiving corticosteroid therapy.

Calcitonin is a naturally occurring peptide which acts via specific receptors to strongly inhibit osteoclast function. It has been used in the treatment of osteoporosis for many years. Historically, calcitonin was administered as a parenteral injection, but the intranasal formulation is now the most widely used because of its improved tolerability. New approaches are currently being investigated to enhance the bioavailability and effects of calcitonin, including oral, pulmonary, and transdermal routes of administration, and novel allosteric activators of the calcitonin receptor.

Several controlled trials have reported that calcitonin stabilizes and in some cases produces a short-term increase in bone density at the lumbar spine level. The most relevant clinical trial to evaluate the effect of calcitonin in the prevention of fractures was the Prevent Recurrence of Osteoporotic Fractures (PROOF) study, a 5-year double-blind, randomized, placebo-controlled trial showing that salmon calcitonin nasal spray at a dosage of 200 IU/day can reduce the risk of vertebral osteoporotic fractures by 33% (relative risk [RR] = 0.67; 95% CI 0.47, 0.97; p = 0.03). However, the 100 and 400 IU/day dosages did not significantly reduce vertebral fracture risk. Effects on nonvertebral fractures were not significant (RR = 0.80; 95% CI 0.59, 1.09; p = 0.16).

There is mounting evidence to show that calcitonin diminishes bone pain in osteoporotic vertebral fractures, which may have clinical utility in vertebral crush fracture syndrome. A recent study suggests that nasal salmon calcitonin appears to be a promising therapeutic approach for the treatment of men with idiopathic osteoporosis, although long-term trials are necessary to confirm these results and evaluate fracture rate as an endpoint in men. The role of calcitonin in corticosteroid-induced osteoporosis remains controversial, hence it can only be considered a second-line agent for the treatment of patients with low bone mineral density who are receiving long-term corticosteroid therapy.

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References

  1. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001; 285: 785–95

    Article  Google Scholar 

  2. Ray NF, Chan JK, Thamer M. Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: report from The National Osteoporosis Fundation. J Bone Miner Res 1997; 12: 24–35

    Article  PubMed  CAS  Google Scholar 

  3. Melton III LJ, Alkinson EJ, Cooper C. Vertebral fractures predict subsequent fractures. Osteoporos Int 1999; 10: 214–21

    Article  PubMed  Google Scholar 

  4. Lindsay R, Silverman SL, Cooper C, et al. Risk of new vertebral fracture in the year following a fracture. JAMA 2001; 285: 320–3

    Article  PubMed  CAS  Google Scholar 

  5. Curry JD. Power law models for the mechanical properties of cancellous bone. Eng Med 1986; 15: 153–4

    Article  Google Scholar 

  6. Wasnich RD, Miller PD. Antifracture efficacy of antiresorptive agents are related to changes in bone density. J Clin Endocrinol Metab 2000; 85: 231–6

    Article  PubMed  CAS  Google Scholar 

  7. Hochberg MC, Greenspan S, Wasnich RD, et al. Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. J Clin Endocrinol Metab 2002 Apr; 87(4): 1586–92

    Article  PubMed  CAS  Google Scholar 

  8. Faulkner KG. Bone matters: are density increases necessary to reduce fracture risk? J Bone Miner Res 2000; 15: 183–7

    Article  PubMed  CAS  Google Scholar 

  9. Delmas PD. How does antiresorptive therapy decrease the risk of fracture in women with osteoporosis? Bone 2000; 27: 1–3

    Article  PubMed  CAS  Google Scholar 

  10. Raisz LG, Au WY, Friedman J, et al. Thyrocalcitonin and bone resorption: studies employing a tissue culture bioassay. Am J Med 1967 Nov; 43(5): 684–90

    Article  PubMed  CAS  Google Scholar 

  11. Friedman J, Raisz LG. Thyrocalcitonin, inhibitor of bone resorption in tissue culture. Science 1967; 150: 1465–7

    Article  Google Scholar 

  12. Chambers TJ, Magnus CJ. Calcitonin alters behaviour of isolated osteoclasts. J Pathol 1982 Jan; 136(1): 27–39

    Article  PubMed  CAS  Google Scholar 

  13. Body JJ. Calcitonin for the long-term prevention and treatment of postmenopausal osteoporosis. Bone 2002 May; 30(5 Suppl.): 75S–9S

    Article  PubMed  CAS  Google Scholar 

  14. Muñoz Torres M, Mezquita Raya P. La calcitonina. Drugs Today (Barc) 1999; 35(s1): 1–12

    Google Scholar 

  15. Plosker GL, McTavish D. Intranasal salcatonin (salmon calcitonin): a review of its pharmacological properties and role in the management of postmenopausal osteoporosis. Drugs Aging 1996 May; 8(5): 378–400

    Article  PubMed  CAS  Google Scholar 

  16. Messer HH, Copp DH. Changes in response to calcitonin following prolonged administration to intact rats. Proc Soc Exp Biol Med 1974; 146: 643–7

    PubMed  CAS  Google Scholar 

  17. Goldring SR, Gorn AH, Yamin M, et al. Characterization of the structural and functional properties of cloned calcitonin receptor cDNAs. Horm Metab Res 1993; 25: 477–80

    Article  PubMed  CAS  Google Scholar 

  18. Zaidi M, Shankar VS, Huang CL-H, et al. Molecular mechanisms of calcitonin action. Endocr J 1994; 2: 459–67

    CAS  Google Scholar 

  19. Alam ASMT, Bax CMR, Shankar VS, et al. Further studies on the mode of action of calcitonin on isolated rat osteoclasts: pharmacological evidence for a second site mediating intracellular Ca2+ mobilization and cell retraction. J Endocrinol 1993; 136: 7–15

    Article  PubMed  CAS  Google Scholar 

  20. Yamin M, Gorn AH, Flannery MR, et al. Cloning and characterization of a mouse brain calcitonin receptor complementary deoxyribonucleic acid and mapping of the calcitonin receptor gene. Endocrinology 1997; 135: 2635–43

    Article  Google Scholar 

  21. Inoue D, Shih C, Galson DL, et al. Calcitonin-dependent down-regulation of the mouse C1a calcitonin receptor in cells of the osteoclast lineage involves a transcriptional mechanism. Endocrinology 1999; 140: 1060–8

    Article  PubMed  CAS  Google Scholar 

  22. Wada S, Akatsu T, Tamura T, et al. Glucocorticoid regulation of calcitonin receptor in mouse osteoclast-like multinucleated cells. J Bone Miner Res 1994; 9: 1705–12

    Article  PubMed  CAS  Google Scholar 

  23. Takahashi S, Goldring SR, Katz M, et al. Downregulation of calcitonin receptor mRNA expression by calcitonin during human osteoclast-like cell differentiation. J Clin Invest 1995; 95: 167–71

    Article  PubMed  CAS  Google Scholar 

  24. Tverberg LA, Gustafson MF, Scott TL, et al. Induction of calcitonin and calcitonin receptor expression in rat mammary tissue during pregnancy. Endocrinology 2000; 141: 3696–702

    Article  PubMed  CAS  Google Scholar 

  25. Jagger C, Chambers TJ, Pondel M. Transgenic mice reveal novel sites of calcitonin receptor gene expression during development. Biochem Biophys Res Commun 2000; 274: 124–9

    Article  PubMed  CAS  Google Scholar 

  26. Kappas S, Clark AJL. Identification of an orphaned receptor gene as a type 1 calcitonin gene-related peptide receptor. Biochem Biophys Res Commun 1995; 217: 832–8

    Article  Google Scholar 

  27. Aiyar N, Rand K, Elshourbagy NA, et al. A cDNA encoding the calcitonin gene-related peptide type-1 receptor. J Biol Chem 1996; 271: 11325–9

    Article  PubMed  CAS  Google Scholar 

  28. Wimalawansa SJ. Calcitonin gene-related peptide and its receptors: molecular genetics, physiology, pathophysiology and therapeutic potential. Endocr Rev 1996; 17: 533–85

    PubMed  CAS  Google Scholar 

  29. Stroop SD, Moore EE. Intracellular calcium increases mediated by a recombinant human calcitonin receptor. J Bone Miner Res 1995; 10: 524–32

    Article  PubMed  CAS  Google Scholar 

  30. Stroop SD, Moore EE, Kuestner RE, et al. Modulation of calcitonin binding by calcium: differential effects of divalent cations. J Recept Res 1993; 13:1173–97

    PubMed  CAS  Google Scholar 

  31. Stroop SD, Thompson DL, Kuestner RE, et al. A recombinant human calcitonin receptor functions as an extracellular calcium sensor. J Biol Chem 1993; 268: 19927–30

    PubMed  CAS  Google Scholar 

  32. Anandathreethavarada HK, Biswas G, Toshiya A, et al. CD38/ADP-ribosyl cyclase: a new role in the regulation of osteoclastic bone resorption. J Cell Biol 1999; 146: 1161–72

    Article  Google Scholar 

  33. Zaidi M, Shankar VS, Adebanjo OA, et al. Regulation of extracellular calcium-sensing in rat osteoclasts by femtomolar calcitonin concentrations. Am J Physiol 1996; 271: F637–44

    PubMed  CAS  Google Scholar 

  34. Zaidi M, Shankar VS, Tunwell RE, et al. A ryanodine receptor-like molecule in the osteoclast plasma membrane is a functional component of the osteoclast Ca2+ sensor. J Clin Invest 1995; 96: 1582–90

    Article  PubMed  CAS  Google Scholar 

  35. Orcell P, Tajima H, Murayama Y, et al. Multiple domains interacting with Gs in the porcine calcitonin receptor. Mol Endocrinol 2000; 14: 170–82

    Article  Google Scholar 

  36. Breimer LH, MacIntyre I, Zaidi M. Peptides from the calcitonin genes: molecular genetics, structure and function. Biochem J 1988; 255: 377–90

    PubMed  CAS  Google Scholar 

  37. Chambers TJ, Magnus CJ. Calcitonin alters behaviour of isolated osteoclasts. J Pathol 1982; 136: 97–106

    Article  Google Scholar 

  38. Holtrop NE, Raisz LJ, Simmons HA. The effects of parathyroid hormone, colchicines and calcitonin on the ultrastructure and the activity of osteoclasts in organ culture. J Cell Biol 1974; 60: 346–55

    Article  PubMed  CAS  Google Scholar 

  39. Kallio DM, Ganat PR, Minkin C. Ultrastructural effects of calcitonin on osteoclasts in tissue culture. J Ultrastruct Res 1972; 39: 205–16

    Article  PubMed  CAS  Google Scholar 

  40. Chambers TJ. Osteoblasts release osteoclasts from calcitonin-induced quiescence. J Cell Sci 1982; 57: 247–53

    PubMed  CAS  Google Scholar 

  41. Zaidi M, Alam ASMT, Shankar VS, et al. A quantitative description of components of in vitro morphometric change in the rat osteoclast model: relationships with cellular function. Eur Biophys J 1992; 21: 349–55

    Article  PubMed  CAS  Google Scholar 

  42. Yumita S, Nicholson GC, Rowe DJ, et al. Biphasic effect of calcitonin on tartrate-resistant acid phosphatase activity in isolated rat osteoclasts. J Bone Miner Res 1991; 6: 591–7

    Article  PubMed  CAS  Google Scholar 

  43. Akisaka T, Gay CV. Ultracytochemical evidence for a proton pump adenosine trisphosphate in chick osteoclasts. Cell Tissue Res 1986; 245: 507–12

    Article  PubMed  CAS  Google Scholar 

  44. Chambers TJ, Fuller K, Darby JA. Hormonal regulation of acid phosphatase release by osteoclasts disaggregated from neonatal rat bone. J Cell Physiol 1987; 132: 90–6

    Article  PubMed  CAS  Google Scholar 

  45. Moonga BS, Moss DW, Patchell A, et al. Intracellular regulation of enzyme secretion from rat osteoclasts and evidence for a functional role in bone resorption. J Physiol 1990; 429: 29–45

    PubMed  CAS  Google Scholar 

  46. Chambers TJ, McSheehy PMJ, Thompson BM, et al. The effect of calcium regulating hormones and prostaglandins on bone resorption by osteoclasts disaggregated from rabbit long bones. Endocrinology 1985; 116: 234–9

    Article  PubMed  CAS  Google Scholar 

  47. Dempster DW, Murills RJ, Horbert W, et al. Biological activity of chicken calcitonin: effects on neonatal rat and embryonic chick osteoclasts. J Bone Miner Res 1987; 2: 443–8

    Article  PubMed  CAS  Google Scholar 

  48. Zaidi M, Fuller K, Bevis PJR, et al. Calcitonin gene-related peptide inhibits osteoclastic bone resorption: a comparative study. Calcif Tissue Int 1987; 40: 149–54

    Article  PubMed  CAS  Google Scholar 

  49. Okubo Y, Bessho K, Fujimura K, et al. Effect of e-calcitonin on osteoinduction by recombinant human bone morphogenetic protein-2. Biochem Biophys Res Commun 2000; 269: 317–21

    Article  PubMed  CAS  Google Scholar 

  50. Wallach S, Rousseau G, Martin L, et al. Effects of calcitonin on animal and in vitro models of skeletal metabolism. Bone 1999; 25: 509–16

    Article  PubMed  CAS  Google Scholar 

  51. Farley J, Dimai HP, Stilt-Coffing B, et al. Calcitonin increases the concentration of insulin-like growth factors in serum-free cultures of human osteoblast-like cells. Calcif Tissue Int 2000; 67: 247–54

    Article  PubMed  CAS  Google Scholar 

  52. Plotkin LI, Weinstein RS, Parfitt AM, et al. Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest 1999; 104: 1363–74

    Article  PubMed  CAS  Google Scholar 

  53. Mancini L, Moradi-Bidhendi N, Brandi ML, et al. Modulation of the effects of osteoprotegrin (OPG) ligand in a human leukemic cell line by OPG and calcitonin. Biochem Biophys Res Commun 2000; 279: 391–7

    Article  PubMed  CAS  Google Scholar 

  54. Agus ZS, Wasserstein S, Goldfarb S. PTH, calcitonin, cyclic nucleotides and the kidney. Annu Rev Physiol 1981; 43: 583–95

    Article  PubMed  CAS  Google Scholar 

  55. Zaidi M, Brain SD, Tippins JR, et al. Structure-activity relationship of human calcitonin gene-related peptide. Biochem J 1990; 269: 775–80

    PubMed  CAS  Google Scholar 

  56. Shinki T, Ueno Y, DeLuca HF, et al. Calcitonin is a major regulator for the expression of renal 25-hydroxyvitaminD3-l-alpha-hydroxylase gene in normocalcemic rats. Proc Natl Acad Sci U S A 1999; 96: 8253–8

    Article  PubMed  CAS  Google Scholar 

  57. Yoshida N, Yoshida T, Nakamura A, et al. Calcitonin induces 25-hydroxyvitamin D3 lalpha hydroxylase mRNA expression via protein kinase C pathway in LLCPK1 cells. J Am Soc Nephrol 1999; 10: 2474–9

    PubMed  CAS  Google Scholar 

  58. Chakraborty M, Chatterjee D, Gorelick FS, et al. Cell cycle dependent kinasespecific regulation of the apical Na/H exchanger and the Na, K-ATPase in the kidney cell line LLCPK1 by calcitonin. Proc Natl Acad Sci U S A 1994; 91: 2115–9

    Article  PubMed  CAS  Google Scholar 

  59. Burckhardt P, Singer FR, Potts Jr JT. Parathyroid function in patients with Paget’s disease treated with salmon calcitonin. Clin Endocrinol 1973; 2: 15–22

    Article  CAS  Google Scholar 

  60. Kraenzlin ME, Seibel MJ, Trechsel U, et al. The effect of intranasal salmon calcitonin on postmenopausal bone turnover as assessed by biochemical markers: evidence of maximal effect after 8 weeks of continuous treatment. Calcif Tissue Int 1996; 58: 216–20

    PubMed  CAS  Google Scholar 

  61. Woodhouse NJ, Mohamedally SM, Saed-Nejad F, et al. Development and significance of antibodies to salmon calcitonin in patients with Paget’s disease on long-term treatment. BMJ 1977 Oct 8; 2(6092): 927–9

    Article  PubMed  CAS  Google Scholar 

  62. Singer FR, Fredericks RS, Minkin C. Salmon calcitonin therapy for Paget’s disease of bone: the problem of acquired clinical resistance. Arthritis Rheum 1980 Oct; 23(10): 1148–54

    Article  PubMed  CAS  Google Scholar 

  63. Levy F, Muff R, Dotti-Sigrist S, et al. Formation of neutralizing antibodies during intranasal synthetic salmon calcitonin treatment of Paget’s disease. J Clin Endocrinol Metab 1988 Sep; 67(3): 541–5

    Article  PubMed  CAS  Google Scholar 

  64. Grauer A, Frank-Raue K, Schroth J, et al. Neutralizing antibodies against salmon calcitonin: rhe cause of a treatment failure in Paget’s disease [in German]. Dtsch Med Wochenschr 1994 Apr 8; 119(14): 507–10

    Article  PubMed  CAS  Google Scholar 

  65. Chesnut III CH, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study: PROOF Study Group. Am J Med 2000; 109: 267–76

    Article  PubMed  CAS  Google Scholar 

  66. Grauer A, Ziegler R, Raue F. Clinical significance of antibodies against calcitonin. Exp Clin Endocrinol Diabetes 1995; 103(6): 345–51

    Article  PubMed  CAS  Google Scholar 

  67. Grauer A, Reinel HH, Lunghall S, et al. Formation of neutralizing antibodies after treatment with human calcitonin. Am J Med 1993 Oct; 95(4): 439–42

    Article  PubMed  CAS  Google Scholar 

  68. Reginster JY, Gaspar S, Deroisy R, et al. Prevention of osteoporosis with nasal salmon calcitonin: effect of anti-salmon calcitonin antibody formation. Osteoporos Int 1993 Sep; 3(5): 261–4

    Article  PubMed  CAS  Google Scholar 

  69. Reginster JY, Azria M, Gaspar S, et al. Endogenous production of specific antibodies does not decrease hypocalcemic response to calcitonin in young rabbits. Calcif Tissue Int 1992 Jun; 50(6): 518–20

    Article  PubMed  CAS  Google Scholar 

  70. Hosking DJ, Denton LB, Cadge B, et al. Functional significance of antibody formation after long-term salmon calcitonin therapy. Clin Endocrinol (Oxf) 1979 Mar; 10(3): 243–52

    Article  CAS  Google Scholar 

  71. Grauer A, Reinel HH, Ziegler R, et al. Neutralizing antibodies against calcitonin. Horm Metab Res 1993 Sep; 25(9): 486–8

    Article  PubMed  CAS  Google Scholar 

  72. Muff R, Dambacher MA, Fischer JA. Formation of neutralizing antibodies during intranasal synthetic salmon calcitonin treatment of postmenopausal osteoporosis. Osteoporos Int 1991 Feb; 1(2): 72–5

    Article  PubMed  CAS  Google Scholar 

  73. Wada S, Udagawa N, Nagata N, et al. Calcitonin receptor down-regulation relates to calcitonin resistance in mature mouse osteoclasts. Endocrinology 1996 Mar; 137(3): 1042–8

    Article  PubMed  CAS  Google Scholar 

  74. Wener JA, Gorton SJ, Raisz LG. Escape from inhibition or resorption in cultures of fetal bone treated with calcitonin and parathyroid hormone. Endocrinology 1972; 90(3): 752–9

    Article  PubMed  CAS  Google Scholar 

  75. Wada S, Udagawa N, Akatsu T, et al. Regulation by calcitonin and glucocorticoids of calcitonin receptor gene expression in mouse osteoclasts. Endocrinology 1997; 138: 521–9

    Article  PubMed  CAS  Google Scholar 

  76. Rakopoulos M, Ikegame M, Findlay DM, et al. Short treatment of osteoclasts in bone marrow culture with calcitonin causes prolonged suppression of calcitonin receptor mRNA. Bone 1995; 17: 447–53

    Article  PubMed  CAS  Google Scholar 

  77. Ikegame M, Rakopoulos M, Martin TJ, et al. Effects of continuous calcitonin treatment on osteoclast-like cell development and calcitonin receptor in mouse bone marrow cultures. J Bone Miner Res 1996; 11: 456–65

    Article  PubMed  CAS  Google Scholar 

  78. Overgaard K, Agnusdei D, Hansen MA, et al. Dose-response bioactivity and bioavailability of salmon calcitonin in premenopausal and postmenopausal women. J Clin Endocrinol Metab 1991; 72: 344–9

    Article  PubMed  CAS  Google Scholar 

  79. Lee WA, Ennis RD, Longenecker JP, et al. The bioavailability of intranasal salmon calcitonin in healthy volunteers with and without a permeation enhancer. Pharm Res 1994 May; 11(5): 747–50

    Article  PubMed  CAS  Google Scholar 

  80. Plosker GL, McTavish D. Intranasal salcatonin (salmon calcitonin): a review of its pharmacological properties and role in the management of postmenopausal osteoporosis. Drugs Aging 1996 May; 8(5): 378–400

    Article  PubMed  CAS  Google Scholar 

  81. Lee YH, Sinko PJ. Oral delivery of salmon calcitonin. Adv Drug Deliv Rev 2000; 42: 225–38

    Article  PubMed  CAS  Google Scholar 

  82. Torres-Lugo M, Peppas NA. Transmucosal delivery systems for calcitonin: a review. Biomaterials 2000; 21: 1191–6

    Article  PubMed  CAS  Google Scholar 

  83. Sakuma S, Hayashi M, Akashi M. Design of nanoparticles composed of graft copolymers for oral peptide delivery. Adv Drug Deliv Rev 2001; 47: 21–37

    Article  PubMed  CAS  Google Scholar 

  84. Millest AJ, Evans JR, Young JJ, et al. Sustained release of salmon calcitonin in vivo from lactide-glycolide copolymer depots. Calcif Tissue Int 1993; 52: 361–4

    Article  PubMed  CAS  Google Scholar 

  85. New R, Littlewood G, Guard P, et al. Intestinal delivery of calcitonin in pig. Int J Pharm 1997; 156: 1–8

    Article  CAS  Google Scholar 

  86. Dogru ST, Calis S, Öner F. Oral multiple w/o/w emulsion formulation of a peptide salmon calcitonin: in vitro-in vivo evaluation. J Clin Pharm Ther 2000; 25: 435–43

    Article  PubMed  CAS  Google Scholar 

  87. Lee YH, Perry BA, Sutyak JP. Regional differences in intestinal spreading and pH recovery and the impact on salmon calcitonin absorption in dogs. Pharmacol Res 2000; 17: 284–90

    Article  CAS  Google Scholar 

  88. Leone-Bay A, Paton DR, Weidner JJ. The development of delivery agents that facilitate the oral absorption of macromolecular drugs. Med Res Rev 2000; 20: 169–86

    Article  PubMed  CAS  Google Scholar 

  89. Buclin T, Cosma Rochat M, Burckhardt P, et al. Bioavailability and biological efficacy of a new oral formulation of salmon calcitonin in healthy volunteers. J Bone Miner Res 2002 Aug; 17(8): 1478–85

    Article  PubMed  CAS  Google Scholar 

  90. Buclin T, Randin JP, Jacquet AF, et al. The effect of rectal and nasal administration of salmon calcitonin in normal subjects. Calcif Tissue Int 1987 Nov; 41(5): 252–8

    Article  PubMed  CAS  Google Scholar 

  91. Overgaard K, Hansen MA, Dirksen KL, et al. Rectal salmon calcitonin for the treatment of postmenopausal osteoporosis. Calcif Tissue Int 1992 Sep; 51(3): 184–8

    Article  PubMed  CAS  Google Scholar 

  92. Kollerup G, Hermann AP, Brixen K, et al. Effects of salmon calcitonin suppositories on bone mass and turnover in established osteoporosis. Calcif Tissue Int 1994 Jan; 54(1): 12–5

    Article  PubMed  CAS  Google Scholar 

  93. Lyritis GP, Ioannidis GV, Karachalios T, et al. Analgesic effect of salmon calcitonin suppositories in patients with acute pain due to recent osteoporotic vertebral crush fractures: a prospective double-blind, randomized, placebo-controlled clinical study. Clin J Pain 1999; 15: 284–9

    Article  PubMed  CAS  Google Scholar 

  94. Chang SL, Hoffman G, Deftos LJ, et al. Transdermal iontophoretic delivery of salmon calcitonin. Int J Pharm 2000; 25: 10–3

    Google Scholar 

  95. Nakamura K, Katagai K, Mori K, et al. Transdermal administration of salmon calcitonin by pulse depolarization-iontophoresis in rats. Int J Pharm 2001 May 7; 218(1–2): 93–102

    Article  PubMed  CAS  Google Scholar 

  96. Chang SL, Hofmann GA, Zhang L, et al. Stability of a transdermal salmon calcitonin formulation. Drug Deliv 2003; 10(1): 41–5

    Article  PubMed  CAS  Google Scholar 

  97. Deftos LJ, Nolan JJ, Seely BL, et al. Intrapulmonary drug delivery of salmon calcitonin. Calcif Tissue Int 1997 Oct; 61(4): 345–7

    Article  PubMed  CAS  Google Scholar 

  98. Reginster JY, Franchimont P. Side-effects of synthetic salmon calcitonin given by intranasal spray compared with intramuscular injection. Clin Exp Rheumatol 1985; 3: 155–7

    PubMed  CAS  Google Scholar 

  99. Hosking DJ. Paget’s disease of bone: an update on management. Drugs 1985; 30: 156–73

    Article  PubMed  CAS  Google Scholar 

  100. Muñoz Torres M, Quesada Charneco M, Torres Vela E, et al. Valoración de la calcitonina nasal e inyectable en la osteoporosis postmenopáusica. REEMO 1994; 3: 9–11

    Google Scholar 

  101. Gennari C, Passeri M, Chierichetti SM, et al. Side-effects of synthetic salmon and human calcitonin. Lancet 1983; I: 594–5

    Article  Google Scholar 

  102. Foti R, Martorana U, Broggini M. Long-term tolerability of nasal spray formulation of salmon calcitonin. Curr Ther Res 1995; 56Suppl. 4: 429–35

    Article  Google Scholar 

  103. Overgaard K, Hansen MA, Jensen SB, et al. Effect of salcatonin given intranasally on bone mass and fracture rates in established osteoporosis: a dose-response study. BMJ 1992; 305: 556–61

    Article  PubMed  CAS  Google Scholar 

  104. Thamsborg G, Storm TL, Sykulski R, et al. Effect of different doses of nasal salmon calcitonin on bone mass. Calcif Tissue Int 1991; 41: 302–7

    Article  Google Scholar 

  105. Reginster JY, Deroisy R, Lecart MP, et al. A double-blind, placebo-controlled, dose-finding trial of intermittent nasal salmon calcitonin for prevention of postmenopausal lumbar spine bone loss. Am J Med 1995; 98: 452–8

    Article  PubMed  CAS  Google Scholar 

  106. Rico H, Revilla M, Hernandez ER, et al. Total and regional bonemineral content and fracture rate in postmenopausal osteoporosis treated with salmon calcitonin: a prospective study. Calcif Tissue Int 1995; 56: 181–5

    Article  PubMed  CAS  Google Scholar 

  107. Stock JL, Avioli LV, Baylink DJ. Calcitonin-salmon nasal sprayreduces the incidence of new vertebral fractures in postmenopausal women: three-year interim results of the PROOF study [abstract 187]. J Bone Miner Res 1997; 12Suppl. 1: S149

    Google Scholar 

  108. Schelemmer A, Ravn P, Hassager C, et al. Morning or evening administration of nasal calcitonin? Effects on biochemical markers of bone turnover. Bone 1997; 20: 63–7

    Article  Google Scholar 

  109. Legrand E, Chappard D, Pascaretti C, et al. Trabecular bone microarchitecture, bone mineral density, and vertebral fractures in male osteoporosis. J Bone Miner Res 2000; 15: 13–9

    Article  PubMed  CAS  Google Scholar 

  110. Ettinger B, Black DM, Mirtlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA 1999; 282: 637–45

    Article  PubMed  CAS  Google Scholar 

  111. Turner CH. Biomechanics of bone: determinants of skeletal fragility and bone quality. Osteoporos Int 2002; 13(2): 97–104

    Article  PubMed  CAS  Google Scholar 

  112. Dempster DW. The impact of bone turnover and bone-active agents on bone quality: focus on the hip. Osteoporos Int 2002 May; 13(5): 349–52

    Article  PubMed  CAS  Google Scholar 

  113. Thamsborg G, Jensen J, Kollerup G, et al. Effect of nasal salmon calcitonin on bone remodeling and bone mass in postmenopausal osteoporosis. Bone 1996; 18: 207–12

    Article  PubMed  CAS  Google Scholar 

  114. Reginster JY, Denis D, Albert A, et al. 1-year controlled randomised trial of prevention of early postmenopausal bone loss by intranasal calcitonin. Lancet 1987; II: 1481–3

    Article  Google Scholar 

  115. Reginster JY, Meurmans L, Deroisy R, et al. A 5-year controlled randomised study of prevention of early postmenopausal trabecular bone loss with nasal salmon calcitonin and calcium. Eur J Clin Invest 1994; 24: 565–9

    Article  PubMed  CAS  Google Scholar 

  116. Overgaard K, Riis BJ, Christiansen C, et al. Effect of salcatonin given intranasally on early postmenopausal bone loss. BMJ 1989; 299: 477–9

    Article  PubMed  CAS  Google Scholar 

  117. Gennari C, Agnusdei D, Montagnani N, et al. An effective regimen of intranasal salmon calcitonin in early postmenopausal bone loss. Calcif Tissue Int 1992; 50: 381–2

    Article  PubMed  CAS  Google Scholar 

  118. Arnala I, Saastamoinen J, Alhava EM. Salmon calcitonin in the prevention of bone loss at perimenopause. Bone 1996; 18: 62–632

    Article  Google Scholar 

  119. Overgaard K, Hansen MA, Nielsen VH, et al. Discontinuous calcitonin treatment of established osteoporosis: effects of withdrawal of treatment. Am J Med 1990; 89: 1–6

    Article  PubMed  CAS  Google Scholar 

  120. Lyritis GP, Magiasis B, Tsakalakos N. Prevention of bone loss in early nonsurgical and nonosteoporotic high turnover patients with salmon calcitonin: the role of biochemical bone markers in monitoring high turnover patients under calcitonin treatment. Calcif Tissue Int 1995; 56: 38–41

    Article  PubMed  CAS  Google Scholar 

  121. Overgaard K, Riis BJ, Christiansen C, et al. Nasal calcitonin for treatment of established osteoporosis. Clin Endocrinol 1989; 30: 435–42

    Article  CAS  Google Scholar 

  122. Ellerington M, Hillard TC, Whitcroft SI, et al. Intranasal salmon calcitonin for the prevention and treatment of postmenopausal osteoporosis. Calcif Tissue Int 1996; 59: 6–11

    Article  PubMed  CAS  Google Scholar 

  123. Rico H, Hernandez ER, Revilla M, et al. Salmon calcitonin reduces vertebral fracture rate in postmenopausal crash fracture syndrome. Bone Miner 1992 Feb; 16(2): 131–8

    Article  PubMed  CAS  Google Scholar 

  124. Hizmetli S, Elden H, Kaptanoglu E, et al. The effect of different doses of calcitonin on bone mineral density and fracture risk in postmenopausal osteoporosis. Int J Clin Pract 1998 Oct; 52(7): 453–5

    PubMed  CAS  Google Scholar 

  125. Silverman SL, Chesnut C, Baylink D, et al. Salmon calcitonin nasal spray is effective and safe in older osteoporotic women: results from the PROOF Study. J Bone Miner Res 2001; 16Suppl. 1: S530–M414

    Google Scholar 

  126. Dempster DW. The contribution of trabecular architecture to cancellous bone quality. J Bone Miner Res 2000; 15: 20–3

    Article  PubMed  CAS  Google Scholar 

  127. Kanis JA, McCloskey EV. Effect of calcitonin on vertebral and other fractures. QJM 1999; 92: 143–9

    Article  PubMed  CAS  Google Scholar 

  128. Cranney A, Tugwell P, Zytarak N, et al. The Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Meta-analyses of therapies for postmenopausal osteoporosis: VI. Meta-analysis of calcitonin for the treatment of postmenopausal osteoporosis. Endocr Rev 2002 Aug; 23(4): 540–51

    Article  PubMed  CAS  Google Scholar 

  129. Cranney A, Guyatt G, Griffith L, et al. The Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Meta-analyses of therapies for postmenopausal osteoporosis. IX: Summary of meta-analysis analyses of therapies for postmenopausal osteoporosis. Endocr Rev 2002 Aug; 23(4): 570–8

    Article  PubMed  CAS  Google Scholar 

  130. Kanis JA, Johnell O, Gullberg B, et al. Evidence of efficacy of drags affecting bone metabolism in preventing hip fracture. BMJ 1992; 305: 1124–8

    Article  PubMed  CAS  Google Scholar 

  131. Lyritis GP, Trovas G. Analgesic effects of calcitonin. Bone 2002 May; 30(5 Suppl. 1): 71–4

    Article  Google Scholar 

  132. Gennari C. Analgesic effect of calcitonin in osteoporosis. Bone 2002 May; 30(5 Suppl. 1): 67–70

    Article  Google Scholar 

  133. Appelboom T. Calcitonin in reflex sympathetic dystrophy syndrome and other painful conditions. Bone 2002 May; 30(5 Suppl.): 84S–6S

    Article  PubMed  CAS  Google Scholar 

  134. Lyritis GP, Paspati I, Karachalios T, et al. Pain relief from nasal salmon calcitonin in osteoporotic vertebral crash fractures: a double-blind, placebo-controlled clinical study. Acta Orthop Scand Suppl 1997; 275: 112–4

    PubMed  CAS  Google Scholar 

  135. Maksymowych WP. Managing acute osteoporotic vertebral fractures with calcitonin. Can Fam Physician 1998 Oct; 44: 2160–6

    PubMed  CAS  Google Scholar 

  136. Pontiroli AE, Pajetta E, Scaglia L, et al. Analgesic effect of intranasal and intramuscular salmon calcitonin in post-menopausal osteoporosis: a double-blind, double-placebo study. Aging (Milano) 1994 Dec; 6(6): 459–63

    CAS  Google Scholar 

  137. Kapuscinski P, Talalaj M, Borowicz J, et al. An analgesic effect of synthetic human calcitonin in patients with primary osteoporosis. Mater Med Pol 1996 Jul–Sep; 28(3): 83–6

    PubMed  CAS  Google Scholar 

  138. Vescovi PP, Pedrazzoni M, Gerra G, et al. Salmon calcitonin given by nasal spray or by injection does not increase beta-endorphin levels in normal men. Life Sci 1990; 47: 1469–73

    Article  PubMed  CAS  Google Scholar 

  139. Braga PC. Calcitonin and its antinociceptive activity: animal and human investigations 1975–1992. Agents Actions 1994; 41: 121–31

    Article  PubMed  CAS  Google Scholar 

  140. Franceschini R, Cataldi A, Barreca T, et al. Plasma beta-endorphin, ACTH and Cortisol secretion in man after nasal spray administration of calcitonin. Eur J Clin Pharmacol 1989; 37: 341–3

    Article  PubMed  CAS  Google Scholar 

  141. Orwoll ES. Osteoporosis in men. Endocrinol Metab Clin North Am 1998 Jun; 27(2): 349–67

    Article  PubMed  CAS  Google Scholar 

  142. Eastell R, Boyle IT, Compston J, et al. Management of male osteoporosis: report of the UK Consensus Group. QJM 1998; 91: 71–92

    Article  PubMed  CAS  Google Scholar 

  143. Trovas GP, Lyritis GP. Aetiology in male osteoporosis. J Bone Miner Res 1997; 12: S1, S370

    Article  Google Scholar 

  144. Kelepouris N, Harper KD, Gannon F. Severe osteoporosis in men. Ann Intern Med 1998; 123: 452–60

    Google Scholar 

  145. Peris P, Guanabens N, Monegal A. Aetiology and presenting symptoms in male osteoporosis. Br J Rheumatol 1995; 34: 936–41

    Article  PubMed  CAS  Google Scholar 

  146. Melton III LJ. Epidemiology of fractures. In: Riggs BL, Melton III LJ, editors. Osteoporosis: etiology, diagnosis and management. New York: Raven Press, 1998: 133–54

    Google Scholar 

  147. Agrawal R, Wallach S, Cohn S, et al. Calcitonin treatment of osteoporosis. In: Pecile A, editor. Calcitonin. Amsterdam: Excerpta Medica, 1981: 237–46

    Google Scholar 

  148. Trovas GP, Lyritis GP, Galanos A, et al. A randomized trial of nasal spray salmon calcitonin in men with idiopathic osteoporosis: effects on bone mineral density and bone markers. J Bone Miner Res 2002 Mar; 17(3): 521–7

    Article  PubMed  CAS  Google Scholar 

  149. Dequeker J, Westhovens R, Luyten FP. Rheumatic disorders and glucocorticoid-induced osteoporosis. Front Horm Res 2002; 30: 107–20

    Article  PubMed  CAS  Google Scholar 

  150. Malerba M, Romanelli G, Grassi V. Glucocorticoid-induced osteoporosis in asthma and respiratory diseases. Front Horm Res 2002; 30: 86–93

    Article  PubMed  CAS  Google Scholar 

  151. Manolagas SC. Corticosteroids and fractures: a close encounter of the third cell kind. J Bone Miner Res 2000 Jun; 15(6): 1001–5

    Article  PubMed  CAS  Google Scholar 

  152. Canalis E, Delany AM. Mechanisms of glucocorticoid action in bone. Ann N Y Acad Sci 2002 Jun; 966: 73–81

    Article  PubMed  CAS  Google Scholar 

  153. Dennison E, Cooper C. Epidemiology of glucocorticoid-induced osteoporosis. Front Horm Res 2002; 30: 121–6

    Article  PubMed  CAS  Google Scholar 

  154. Van Staa TP, Leufkens HG, Abenhaim L, et al. Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology (Oxford) 2000 Dec; 39(12): 1383–9

    Article  Google Scholar 

  155. Sambrook PN, Birmingham J, Kelly P, et al. Prevention of corticosteroid osteoporosis: a comparison of calcium, calcitriol, and calcitonin. N Engl J Med 1993; 328: 1747–52

    Article  PubMed  CAS  Google Scholar 

  156. Healey JH, Paget SA, Williams-Russo P, et al. A randomized controlled trial of salmon calcitonin to prevent bone loss in corticosteroid-treated temporal arteritis and polymyalgia rheumatica. Calcif Tissue Int 1996; 58: 73–80

    Article  PubMed  CAS  Google Scholar 

  157. Adachi JD, Bensen WG, Bell MJ, et al. Salmon calcitonin nasal spray and the prevention of corticosteroid-induced osteoporosis. Br J Rheumatol 1997; 36: 255–9

    Article  PubMed  CAS  Google Scholar 

  158. Luengo M, Pons F, Martinez de Osaba JM, et al. Prevention of further bone mass loss by nasal calcitonin in patients on long term glucocorticoid therapy for asthma: a two year follow up study. Thorax 1994; 49: 1099–102

    Article  PubMed  CAS  Google Scholar 

  159. Kotaniemi A, Piirainen H, Paimela L, et al. Is continuous intranasal salmon calcitonin effective in treating axial bone loss in patients with active RA receiving low-dose glucocorticoid? J Rheumatol 1996; 23: 1875–9

    PubMed  CAS  Google Scholar 

  160. Ringe JD, Welzel D. Salmon calcitonin in the therapy of corticosteroid-induced osteoporosis. Eur J Clin Pharmacol 1987; 33: 35–9

    Article  PubMed  CAS  Google Scholar 

  161. Luengo M, Picado C, Del Rio L, et al. Treatment of steroid-induced osteopenia with calcitonin in corticosteroid-dependent asthma. Am Rev Respir Dis 1990; 142: 104–7

    PubMed  CAS  Google Scholar 

  162. Cranney A, Welch V, Adachi JD, et al. Calcitonin for the treatment and prevention of corticosteroid-induced osteoporosis. Cochrane Database Syst Rev 2000; (2): CD001983

  163. Canalis E, Giustina A. Glucocorticoid-induced osteoporosis: summary of a workshop. J Clin Endocrinol Metab 2001 Dec; 86(12): 5681–5

    Article  PubMed  CAS  Google Scholar 

  164. Yeap SS, Hosking DJ. Management of corticosteroid-induced osteoporosis. Rheumatology (Oxford) 2002 Oct; 41(10): 1088–94

    Article  CAS  Google Scholar 

  165. Roux C, Dougados M. Calcitonin in glucocorticoid-induced osteoporosis. Front Horm Res 2002; 30: 145–9

    Article  PubMed  CAS  Google Scholar 

  166. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-induced Osteoporosis. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. Arthritis Rheum 2001 Jul; 44(7): 1496–503

    Article  Google Scholar 

  167. Leuthauser K, Gujer R, Aldecoa A, et al. Receptor-activity-modifying protein 1 forms heterodimers with two G-protein-coupled receptors to define ligand recognition. Biochem J 2000; 2: 347–51

    Article  Google Scholar 

  168. Samura A, Wada S, Suda S, et al. Calcitonin receptor regulation and responsiveness to calcitonin in human osteoclast-like cells prepared in vitro using receptor activator of nuclear factor kappaB ligand and macrophage colony-stimulating factor. Endocrinology 2000; 141: 3774–82

    Article  PubMed  CAS  Google Scholar 

  169. Suva LJ, Flannery MS, Caulfield MP, et al. Design, synthesis and utility of novel benzophenone-containing calcitonin analogs for photoaffinity labeling the calcitonin receptor. J Pharmacol Exp Ther 1997; 283: 876–88

    PubMed  CAS  Google Scholar 

  170. Armour SL, Foord S, Kenakin T, et al. Pharmacological characterization of receptor-activity-modifying proteins (RAMPs) and the human calcitonin receptor. J Pharmacol Toxicol Methods 1999; 42: 217–24

    Article  PubMed  CAS  Google Scholar 

  171. Collins MT, Skarulis MC, Bilezikian JP, et al. Treatment of hypercalcemia secondary to parathyroid carcinoma with a novel calcimimetic agent. J Clin Endocrinol Metab 1998; 83: 1083–8

    Article  PubMed  CAS  Google Scholar 

  172. Goodman WG, Frazao JM, Goodkin DA, et al. A calcimimetic agent lowers plasma parathyroid hormone levels in patients with secondary hyperparathyroidism. Kidney Int 2000; 58: 436–45

    Article  PubMed  CAS  Google Scholar 

  173. Silverberg SJ, Bone HG, Marriott TB, et al. Short term inhibition of parathyroid hormone secretion by a calcium receptor agonist in patients with primary hyperparathyroidism. N Engl J Med 1997; 337: 1506–10

    Article  PubMed  CAS  Google Scholar 

  174. Shoback DM, Bilezikian JP, Turner SA, et al. The calcimimetic cinacalcet normalizes serum calcium in subjects with primary hyperparathyroidism. J Clin Endocrinol Metab 2003; 88(12): 5644–9

    Article  PubMed  CAS  Google Scholar 

  175. Morley P, Whitfield JF, Willick GE. Parathyroid hormone: an anabolic treatment for osteoporosis. Curr Pharm Des 2001; 7: 671–87

    Article  PubMed  CAS  Google Scholar 

  176. Neer RM, Arnaud CD, Zanchetta JR. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001; 344: 1434–41

    Article  PubMed  CAS  Google Scholar 

  177. Hodsman AB, Fraher LJ. Biochemical responses to sequential human parathyroid hormone (1–38) and calcitonin in osteoporotic patients. Bone Miner 1990 May; 9(2): 137–52

    Article  PubMed  CAS  Google Scholar 

  178. Hodsman AB, Steer BM, Fraher LJ, et al. Bone densitometric and histomorphometric responses to sequential human parathyroid hormone (1–38) and salmon calcitonin in osteoporotic patients. Bone Miner 1991 Jul; 14(1): 67–83

    Article  PubMed  CAS  Google Scholar 

  179. Hodsman AB, Fraher LJ, Ostbye T, et al. An evaluation of several biochemical markers for bone formation and resorption in a protocol utilizing cyclical parathyroid hormone and calcitonin therapy for osteoporosis. J Clin Invest 1993 Mar; 91(3): 1138–48

    Article  PubMed  CAS  Google Scholar 

  180. Hodsman AB, Fraher LJ, Watson PH, et al. A randomized controlled trial to compare the efficacy of cyclical parathyroid hormone versus cyclical parathyroid hormone and sequential calcitonin to improve bone mass in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 1997 Feb; 82(2): 620–8

    Article  PubMed  CAS  Google Scholar 

  181. DeLuca PP, Dani BA. Skeletal effects of parathyroid hormone (1–34) in ovariectomized rats with or without concurrent administration of salmon calcitonin. AAPS PharmSci 2001; 3(4): E27

    PubMed  CAS  Google Scholar 

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Acknowledgements

This work was partially supported by a grant from Fondo de Investigación Sanitaria (FIS PI021089).

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  1. Bone Metabolic Unit, Endocrinology Division, Hospital Universitario San Cecilio, Granada, 18012, Spain

    Manuel Muñoz-Torres, Guillermo Alonso & Pedro Mezquita Raya

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  1. Manuel Muñoz-Torres
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Correspondence to Manuel Muñoz-Torres.

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Muñoz-Torres, M., Alonso, G. & Mezquita Raya, P. Calcitonin Therapy in Osteoporosis. Mol Diag Ther 3, 117–132 (2004). https://doi.org/10.2165/00024677-200403020-00006

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