Salmon calcitonin: a review of current and future therapeutic indications

Salmon calcitonin, available as a therapeutic agent for more than 30 years, demonstrates clinical utility in the treatment of such metabolic bone diseases as osteoporosis and Paget's disease, and potentially in the treatment of osteoarthritis. This review considers the physiology and pharmacology of salmon calcitonin, the evidence based research demonstrating efficacy and safety of this medication in postmenopausal osteoporosis with potentially an effect on bone quality to explain its abilities to reduce the risk of spine fracture, the development of an oral salmon calcitonin preparation, and the therapeutic rationale for this preparation's chondroprotective effect in osteoarthritis.

[1]  C. Christiansen,et al.  NASAL CALCITONIN FOR TREATMENT OF ESTABLISHED OSTEOPOROSIS , 1989, Clinical endocrinology.

[2]  A. Kriegman,et al.  Acute Effects of Calcitonin Nasal Spray on Serum C-telopeptide of Type 1 Collagen (CTx) Levels in Elderly Osteopenic Women with Increased Bone Turnover , 2004, Calcified Tissue International.

[3]  M. Suarez‐Almazor,et al.  Calcitonin for preventing and treating corticosteroid‐induced osteoporosis , 2000 .

[4]  E. Siris.  Goals of treatment for paget's disease of bone , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[5]  L. Laurian,et al.  Calcitonin Induced Increase in ACTH, β-Endorphin and Cortisol Secretion , 1986 .

[6]  M. Karsdal,et al.  Calcitonin is involved in cartilage homeostasis: is calcitonin a treatment for OA? , 2006, Osteoarthritis and cartilage.

[7]  E. McCloskey,et al.  Medical Management of Hypercalcemia , 2003, Calcified Tissue International.

[8]  O. Johnell,et al.  Evidence for efficacy of drugs affecting bone metabolism in preventing hip fracture. , 1992, BMJ.

[9]  Charles A Cefalu,et al.  Is bone mineral density predictive of fracture risk reduction? , 2004, Current medical research and opinion.

[10]  Chang Lw,et al.  Analgesic effect of intranasal salmon calcitonin in the treatment of osteoporotic vertebral fractures. , 1989 .

[11]  H. Suominen,et al.  Randomized, Double-Blind, Clinically Controlled Trial of Intranasal Calcitonin Treatment in Patients with Hip Fracture , 2002, Calcified Tissue International.

[12]  E. Thonar,et al.  Treatment with calcitonin suppresses the responses of bone, cartilage, and synovium in the early stages of canine experimental osteoarthritis and significantly reduces the severity of the cartilage lesions. , 1999, Arthritis and rheumatism.

[13]  L. Avioli,et al.  Bone turnover in postmenopausal osteoporosis. Effect of calcitonin treatment. , 1988, The Journal of clinical investigation.

[14]  N. Watts,et al.  Review of Treatment Modalities for Postmenopausal Osteoporosis , 2005, Southern medical journal.

[15]  B. Riis,et al.  Discontinuous calcitonin treatment of established osteoporosis--effects of withdrawal of treatment. , 1990, The American journal of medicine.

[16]  G. Conforto,et al.  Role of serotonin in the analgesic activity of calcitonin. , 1984, European journal of pharmacology.

[17]  P. Härkönen,et al.  Calcitonin promotes osteoclast survival in vitro , 1996, Molecular and Cellular Endocrinology.

[18]  J. Stepan,et al.  Plasma type 1 collagen cross-linked C-telopeptide: a sensitive marker of acute effects of salmon calcitonin on bone resorption. , 2002, Clinica chimica acta; international journal of clinical chemistry.

[19]  A. Jullienne,et al.  Calcitonin receptor polymorphism is associated with a decreased fracture risk in post-menopausal women. , 1998, Human molecular genetics.

[20]  S. Posen,et al.  PAGET'S DISEASE OF BONE EXPERIENCES WITH 100 PATIENTS TREATED WITH SALMON CALCITONIN ∗ , 1981, The Medical journal of Australia.

[21]  J. Reginster,et al.  Long‐term (3 years) prevention of trabecular postmenopausal bone loss with low‐dose intermittent nasal salmon calcitonin , 1994, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[22]  F. Kolb,et al.  Synthetic salmon calcitonin. Treatment of Paget's disease and osteogenesis imperfecta. , 1972, JAMA.

[23]  M. A. Hansen,et al.  Effect of salcatonin given intranasally on bone mass and fracture rates in established osteoporosis: a dose-response study. , 1992, BMJ.

[24]  M. Suarez‐Almazor,et al.  Calcitonin for the treatment and prevention of corticosteroid-induced osteoporosis. , 2000, The Cochrane database of systematic reviews.

[25]  A. Fitton,et al.  Intranasal Salmon Calcitonin , 1991 .

[26]  G. Thamsborg,et al.  Acute effects of nasal salmon calcitonin on calcium and bone metabolism , 1993, Calcified Tissue International.

[27]  T. Buclin,et al.  Bioavailability and Biological Efficacy of a New Oral Formulation of Salmon Calcitonin in Healthy Volunteers , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[28]  P. Geusens,et al.  Femoral Neck Trabecular Microstructure in Ovariectomized Ewes Treated With Calcitonin: MRI Microscopic Evaluation , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[29]  H. Rico,et al.  Intranasal Salcatonin (Salmon Calcitonin) A Review of its Pharmacological Properties and Role in the Management of Postmenopausal Osteoporosis , 1996 .

[30]  C. Christiansen,et al.  Effects of Oral Ibandronate Administered Daily or Intermittently on Fracture Risk in Postmenopausal Osteoporosis , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[31]  A. Chines,et al.  Risedronate preserves bone architecture in postmenopausal women with osteoporosis as measured by three-dimensional microcomputed tomography. , 2004, Bone.

[32]  J. Reginster,et al.  Evidence-based guidelines for the treatment of postmenopausal osteoporosis: a consensus document of the Belgian Bone Club , 2005, Osteoporosis International.

[33]  T. Buclin,et al.  The effect of rectal and nasal administration of salmon calcitonin in normal subjects , 1987, Calcified Tissue International.

[34]  C. Christiansen,et al.  Safety and Efficacy of a Novel Salmon Calcitonin (sCT) Technology‐Based Oral Formulation in Healthy Postmenopausal Women: Acute and 3‐Month Effects on Biomarkers of Bone Turnover , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[35]  T. Vokes,et al.  Treatment of postmenopausal osteoporosis. , 2001, JAMA.

[36]  S. Hilsenbeck,et al.  Downregulation of calcitonin receptor mRNA expression by calcitonin during human osteoclast-like cell differentiation. , 1995, The Journal of clinical investigation.

[37]  D. Kiel,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. , 2000, The American journal of medicine.

[38]  G. Lyritis,et al.  Analgesic effect of Salmon calcitonin in osteoporotic vertebral fractures: A double-blind placebo-controlled clinical study , 1991, Calcified Tissue International.

[39]  M. Karsdal,et al.  Oral salmon calcitonin induced suppression of urinary collagen type II degradation in postmenopausal women: a new potential treatment of osteoarthritis. , 2005, Bone.

[40]  H K Genant,et al.  Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. , 1999, JAMA.

[41]  J. Hoehns,et al.  Analgesic Efficacy of Calcitonin for Vertebral Fracture Pain , 2003, The Annals of pharmacotherapy.

[42]  S. Cummings,et al.  Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures , 1996, The Lancet.

[43]  S. Wallach,et al.  Effects of calcitonin on bone quality and osteoblastic function , 1993, Calcified Tissue International.

[44]  M. Revilla,et al.  Salmon calcitonin reduces vertebral fracture rate in postmenopausal crush fracture syndrome. , 1992, Bone and mineral.

[45]  C C Glüer,et al.  Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. , 1999, JAMA.

[46]  A. Bradley,et al.  Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene. , 2002, The Journal of clinical investigation.

[47]  B. Rowe,et al.  Calcitonin for treating acute pain of osteoporotic vertebral compression fractures: a systematic review of randomized, controlled trials , 2005, Osteoporosis International.

[48]  Dennis M. Black,et al.  Relationships between bone mineral density and incident vertebral fracture risk with raloxifene therapy , 2002 .

[49]  K. Väänänen,et al.  Mechanism of osteoclast mediated bone resorption--rationale for the design of new therapeutics. , 2005, Advanced drug delivery reviews.

[50]  M. Passeri,et al.  Effects of salmon calcitonin in postmenopausal osteoporosis: A controlled double-blind clinical study , 2007, Calcified Tissue International.

[51]  T. Chambers,et al.  Calcitonin alters behaviour of isolated osteoclasts , 1982, The Journal of pathology.

[52]  A. Gozzini,et al.  Association of low bone mass with vitamin d receptor gene and calcitonin receptor gene polymorphisms in juvenile idiopathic arthritis. , 2002, The Journal of rheumatology.

[53]  A. Galanos,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. , 1999, The Clinical journal of pain.

[54]  P. Crosignani,et al.  Effect of hormone replacement therapy and calcitonin on bone mass in postmenopausal women. , 1992, European journal of obstetrics, gynecology, and reproductive biology.

[55]  S. Sagar,et al.  Calcitonin: regional distribution of the hormone and its binding sites in the human brain and pituitary. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[56]  G. Lyritis,et al.  Pain relief from nasal salmon calcitonin in osteoporotic vertebral crush fractures. A double blind, placebo-controlled clinical study. , 1997, Acta orthopaedica Scandinavica. Supplementum.

[57]  H. Genant,et al.  Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. , 2003, Bone.

[58]  A. Griesmacher,et al.  Salmon calcitonin nasal spray treatment for postmenopausal women after hip fracture with total hip arthroplasty , 2004, Journal of Bone and Mineral Metabolism.

[59]  L. Wisneski.  Salmon calcitonin in the acute management of hypercalcemia , 2007, Calcified Tissue International.

[60]  T. Chambers,et al.  The sensitivity of isolated osteoclasts to morphological transformation by calcitonin. , 1983, The Journal of clinical endocrinology and metabolism.

[61]  John P. Bilezikian,et al.  Principles of Bone Biology , 1996 .

[62]  S. Silverman.  Quality-of-life issues in osteoporosis , 2005, Current rheumatology reports.

[63]  S. Silverman,et al.  Rationale for the potential use of calcitonin in osteoarthritis. , 2005, Journal of musculoskeletal & neuronal interactions.

[64]  V. Fornasier,et al.  Histologic changes in Paget's disease treated with calcitonin. , 1978, Human pathology.

[65]  B. Riis,et al.  Effect of salcatonin given intranasally on early postmenopausal bone loss. , 1989, BMJ.

[66]  K. Pun,et al.  Analgesic effect of intranasal salmon calcitonin in the treatment of osteoporotic vertebral fractures. , 1989, Clinical therapeutics.

[67]  D. Copp,et al.  Demonstration of a Hypocalcemic Factor (Calcitonin) in Commercial Parathyroid Extract , 1961, Science.

[68]  A. Schulz,et al.  Changes of bone remodelling surfaces and bone structure in Paget's disease following long-term treatment with calcitonin , 1976, Calcified Tissue Research.

[69]  I. B. Bender.  Paget's disease. , 2003, Journal of endodontics.

[70]  R. Portenoy,et al.  Adjuvant analgesics in cancer pain management. , 2004, The oncologist.

[71]  C. Chesnut,et al.  Perspective: Reconsidering the Effects of Antiresorptive Therapies in Reducing Osteoporotic Fracture , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[72]  M. Zaidi,et al.  Forty years of calcitonin--where are we now? A tribute to the work of Iain Macintyre, FRS. , 2002, Bone.

[73]  J. A. Strong,et al.  Treatment of Paget's Disease of Bone with Synthetic Salmon Calcitonin , 1974, British medical journal.

[74]  D. Baylink,et al.  The anti-bone-resorptive agent calcitonin also acts in vitro to directly increase bone formation and bone cell proliferation. , 1988, Endocrinology.

[75]  D. Newitt,et al.  Effects of Salmon Calcitonin on Trabecular Microarchitecture as Determined by Magnetic Resonance Imaging: Results From the QUEST Study , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[76]  S. Silverman,et al.  The Analgesic Role of Calcitonin Following Osteoporotic Fracture , 2002, Osteoporosis International.

[77]  M. Zaidi,et al.  Molecular and Clinical Pharmacology of Calcitonin , 2002 .

[78]  Harry K. Genant,et al.  Reduction of Vertebral Fracture Risk in Postmenopausal Women With Osteoporosis Treated With Raloxifene: Results From a 3-year Randomized Clinical Trial , 2000 .

[79]  P. Sexton.  Central nervous system binding sites for calcitonin and calcitonin gene-related peptide , 1991, Molecular Neurobiology.

[80]  E. McCloskey,et al.  The effect of intranasal salmon calcitonin therapy on bone mineral density in idiopathic male osteoporosis without vertebral fractures--an open label study. , 2005, Bone.

[81]  J. Adachi,et al.  Early effects of raloxifene on clinical vertebral fractures at 12 months in postmenopausal women with osteoporosis. , 2002, Archives of internal medicine.

[82]  S. Antonarakis,et al.  Linkage map of the short arm of human chromosome 11: location of the genes for catalase, calcitonin, and insulin-like growth factor II. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[83]  T. Spector,et al.  Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies , 2004, The New England journal of medicine.

[84]  P. Roberson,et al.  Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. , 1999, The Journal of clinical investigation.

[85]  R. Civitelli,et al.  Analgesic activity of salmon anf human calcitonin against cancer pain: a double-blind. placebo-controlled clinical study , 1985 .

[86]  P. F. Hirsch,et al.  Is calcitonin an important physiological substance? , 2003, Endocrine.

[87]  T. Martin,et al.  Biphasic effect of calcitonin on tartrate‐resistant acid phosphatase activity in isolated rat osteoclasts , 1991, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[88]  G. Thamsborg.  Effect of nasal salmon calcitonin on calcium and bone metabolism. , 1999, Danish medical bulletin.

[89]  G. Kwakkel,et al.  Treatment of reflex sympathetic dystrophy (CRPS type 1): a research synthesis of 21 randomized clinical trials. , 2001, Journal of pain and symptom management.

[90]  S. Krane,et al.  An evaluation of antibodies and clinical resistance to salmon calcitonin. , 1972, The Journal of clinical investigation.

[91]  D. H. Copp,et al.  25 Years of salmon calcitonin: From synthesis to therapeutic use , 1995, Calcified Tissue International.

[92]  C. Johnston,et al.  Effects of calcitonin in Paget's disease and polyostotic fibrous dysplasia. , 1970, The Journal of clinical endocrinology and metabolism.

[93]  T. Fujita,et al.  Bone-anabolic effect of salmon calcitonin on glucocorticoid-induced osteopenia in rats. , 2000, Biological & pharmaceutical bulletin.

[94]  T. Ogihara,et al.  Calcitonin Receptor Gene Polymorphism in Japanese Women: Correlation with Body Mass and Bone Mineral Density , 2001, Calcified Tissue International.

[95]  K. Dewbury,et al.  Paget's disease. Radiological changes occurring in untreated patients and those on therapy with salmon calcitonin during two years' observation. , 1977, The British journal of radiology.

[96]  P. Kulkarni,et al.  Antirsesorptive treatment of postmenopausal osteoporosis: review of randomized clinical studies and rationale for the Evista alendronate comparison (EVA) trial , 2004, Current medical research and opinion.

[97]  M. Holtrop,et al.  THE EFFECTS OF PARATHYROID HORMONE, COLCHICINE, AND CALCITONIN ON THE ULTRASTRUCTURE AND THE ACTIVITY OF OSTEOCLASTS IN ORGAN CULTURE , 1974, The Journal of cell biology.

[98]  E. Hernández,et al.  Biochemical assessment of acute and chronic treatment of Paget's bone disease with calcitonin and calcium with and without biphosphonate. , 1988, Bone.

[99]  W. Maksymowych.  Managing acute osteoporotic vertebral fractures with calcitonin. , 1998, Canadian family physician Medecin de famille canadien.

[100]  A. Galanos,et al.  A Randomized Trial of Nasal Spray Salmon Calcitonin in Men With Idiopathic Osteoporosis: Effects on Bone Mineral Density and Bone Markers , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[101]  M. Hooper,et al.  Randomized Trial of the Effects of Risedronate on Vertebral Fractures in Women with Established Postmenopausal Osteoporosis , 2000, Osteoporosis International.

[102]  H. Kruse,et al.  [Treatment of Paget's disease of bone with salmon calcitonin (author's transl)]. , 2008, Deutsche medizinische Wochenschrift.

[103]  R. Foti,et al.  Long-term tolerability of nasal spray formulation of salmon calcitonin , 1995 .

[104]  D. Hosking,et al.  Comparison of the renal and skeletal actions of calcitonin in the treatment of severe hypercalcaemia of malignancy. , 1984, The Quarterly journal of medicine.

[105]  Antiresorptive treatment of postmenopausal osteoporosis: comparison of study designs and outcomes in large clinical trials with fracture as an endpoint. , 2002, Endocrine reviews.

[106]  M. Colado,et al.  Involvement of central serotonergic pathways in analgesia elicited by salmon calcitonin in the mouse. , 1994, European journal of pharmacology.

[107]  F. Aubin,et al.  Equivalence of Nasal Spray and Subcutaneous Formulations of Salmon Calcitonin , 1997, Calcified Tissue International.