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Paget’s Disease of Bone

An Update on Management

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Summary

The essential requirement for effective treatment of Paget’s disease of bone is that the characteristic abnormality of bone remodelling is predictably corrected without the occurrence of significant side effects. Although the ideal agent is not currently available, appropriate use of the calcitonins or diphosphonates goes a long way to achieving this goal. Calcitonin (50 to 100 MRC units subcutaneously daily or 3 times weekly) will generally reduce bone turnover by approximately 50% within 6 months. However, very active disease will not be controlled and bone turnover will generally increase once treatment is withdrawn. Calcitonin is without significant side effects, although some patients will develop antibody-mediated resistance to the exogenous calcitonin species. An advantage of calcitonin is that there is radiographic evidence of a return to normal bone remodelling during treatment.

Although a number of diphosphonates (now more correctly termed bisphosphonates) are available for experimental use, only the first generation compound, disodium etidronate (EHDP) is commercially available. It too will reduce bone turnover by about 50% within 6 months when given in a dose of 5 mg/kg daily. Unlike calcitonin, it results in a more sustained control of bone turnover while having the additional advantage that it can be given by mouth. Although larger doses are more effective in controlling very active disease, there is a real risk of causing defective bone mineralisation which may result in the development of atraumatic long bone fractures or diffuse bone pains. Combinations of calcitonin and disodium etidronate in conventional dosage seem to result in an additive suppressant effect on bone turnover and may be indicated for more active disease. Advances in treatment are progressing rapidly and it seems likely that in the next few years the introduction of new agents for the control of Paget’s disease will more nearly approach the ideal goal of treatment.

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References

  • Altman, P.D.; Johnson, C.C.; Khairi, M.R.A., Wellman, H.N., Scrafini, A.N. and Sankey, R.R.: Influence of disodium etidronate on clinical and laboratory manifestations of Pagets disease of bone (osteitis deformans). New England Journal of Medicine 289: 1379–1384 (1973).

    PubMed  CAS  Google Scholar 

  • Avramides, A.; Baker, R.K. and Wallach, S.: Metabolic effects of synthetic salmon calcitonin in Pagets disease of bone. Metabolism 23: 1037–1046 (1974).

    PubMed  CAS  Google Scholar 

  • Avramides, A.; Flores, A.; De Rose, J. and Wallach, S.: Treatment of Pagets disease of bone with once a week injections of salmon calcitonin. British Medical Journal 3: 632 (1975).

    PubMed  CAS  Google Scholar 

  • Avramides, A.. Flores, A.; De Rose, J. and Wallach, S.: Pagets disease of bone: Observations after cessation of long term synthetic salmon calcitonin treatment. Journal of Clinical Endocrinology and Metabolism 42: 459–463 (1976).

    PubMed  CAS  Google Scholar 

  • Barry, H.C.: Page’s Disease of Bone (Livingstone, Edinburgh 1969).

    Google Scholar 

  • Bijvoet, O.L.M.; Frijlink, W.B.; Jie, K.; van der Linden, H.; Meijer, C.J.L.M. et al.: APD in Paget’s disease of bone: Role of the mononuclear phagocyte system? Arthritis and Rheumatism 23: 1193–1204 (1980).

    PubMed  CAS  Google Scholar 

  • Bijvoet, O.L.M.; Hosking, D.J.; Frijlink, W.B.; TeVelde, J. and Vellenga, C.J.L.R.: Treatment of Page’s disease with combined calcitonin and diphosphonate (EHDP). Metabolic Bone Disease and Related Research 1: 251–261 (1978).

    Google Scholar 

  • Borie, A.B.: Calcium metabolism at the cellular level. Federation Proceedings. 32: 1944–1950 (1973).

    Google Scholar 

  • Bouvet, J.P.: Traitement de la maladie de Paget par la thyrocalcitonine de saumon. Etude cooperative en double insu. Nouvelle Presse Médicale 6: 1447–1450 (1977).

    Google Scholar 

  • Bowie, H.C. and Kanis, J.A.: Calcitonin in the assessment and preparation of patients with Paget’s disease for surgery; in Kanis (Ed.) Bone Disease and Calcitonin, pp. 61–69 (Armour Pharmaceutical, Eastbourne 1977).

    Google Scholar 

  • Burckhardt, P.; Ducommun, J. and Hessler, C: Treatment of Paget’s disease with human calcitonin; in MacIntyre (Ed.) Human Calcitonin and Paget’s disease, pp. 155–166 (Hans Huber, Berne 1977).

    Google Scholar 

  • Burckhardt, P.M.; Singer, F.R. and Potts Jr, J.T.: Parathyroid function in patients with Paget’s disease treated with salmon calcitonin. Clinical Endocrinology 2: 15–22 (1973).

    PubMed  CAS  Google Scholar 

  • Canfield, R.; Rosner, W.; Skinner, J.; McWhorter, J.; Resnick, L. et al.: Diphosphonate therapy of Paget’s disease of bone. Journal of Clinical Endocrinology and Metabolism 44: 96–106 (1977).

    PubMed  CAS  Google Scholar 

  • Chambers, T.J.: The cellular basis of bone resorption. Clinical Orthopaedics and Related Research 151: 283–293 (1980).

    PubMed  Google Scholar 

  • Chambers, T.J. and Magnus, C.J.: Calcitonin alters behaviour of isolated osteoclasts. Journal of Pathology 136: 27–39 (1982).

    PubMed  CAS  Google Scholar 

  • Chapuy, M.C; Meunier, P.J. and Alexandre, C: Comparison of the acute effects of human and salmon calcitonin in Pagetic patients in relation with plasma calcitonin levels. Metabolic Bone Disease and Related Research 2: 93–98 (1980).

    Google Scholar 

  • Chen, J.R.; Rhee, R.S.C; Wallach, S.; Avramides, A. and Flores, A.: Neurologic disturbances in Paget’s disease of bone. Responses to calcitonin. Neurology 29: 448–457 (1979).

    PubMed  CAS  Google Scholar 

  • Collins, D.H.: Pagets disease of bone incidence and subclinical forms. Lancet 2: 51–57 (1976).

    Google Scholar 

  • Condon, J.R.: Glucagon in the treatment of Paget’s disease of bone. British Medical Journal 4: 719–721 (1971).

    PubMed  CAS  Google Scholar 

  • Cooper, C.W.; Peng, T.-C; Toverud, S.U.; Vander-Wiel, C.J. and Talmage, R.V.: Calcitonin and feeding; in Cohn et al. (Eds) Hormonal Control of Calcium Metabolism, Internal Congress Series 511. pp. 271–280 (Excerpta Medica, Amsterdam 1981).

    Google Scholar 

  • Deftos, L.J.; Burton, D.; Catherwood, B.D.; Bone, H.G.; Parthemore, J.G. et al.: Demonstration by immunoperoxidase histochemistry of calcitonin in the anterior lobe of the rat pituitary. Journal of Clinical Endocrinology and Metabolism 47: 457–460 (1978).

    PubMed  CAS  Google Scholar 

  • De Rose, J.; Singer, F.R.; Avramides, A.; Flores, A.; Dziadiw, R. et al.: Response of Paget’s disease to porcine and salmon calcitonins. American Journal of Medicine 56: 858–866 (1974).

    Google Scholar 

  • DeVries, H.R. and Bijvoet, O.L.M.: Results of prolonged treatment of Paget’s disease of bone with disodium ethane-l-hydroxy-1,1-diphosphonate (EHDP). Netherlands Journal of Medicine 17: 281–297 (1974).

    CAS  Google Scholar 

  • Douglas, D.L.; Duckworth, T.; Kanis, J.A.; Preston, D.; Beard, D.J. et al.: Biochemical and clinical responses to dichloromethylene diphosphonate (Cl2MDP) in Paget’s disease of bone. Arthritis and Rheumatism 23: 1185–1192 (1980).

    PubMed  CAS  Google Scholar 

  • Douglas, D.L.; Kanis, J.A.; Duckworth, T.; Beard, D.J.; Paterson, A.D. and Russell, R.G.G.: Paget’s disease. Improvement of spinal cord dysfunction with diphosphonates and calcitonin. Metabolic Bone Disease and Related Research 3: 327–335 (1981).

    CAS  Google Scholar 

  • Dove, J.: Complete fractures of the femur in Paget’s disease of bone. Journal of Bone and Joint Surgery 62B: 12–17 (1980).

    Google Scholar 

  • Doyle, F.R.; Pennock, J.; Greenberg, P.B.; Joplin, G.F. and Maclntyre, L.: Radiological evidence of a dose related response to longterm treatment of Paget’s disease with human calcitonin. British Journal of Radiology 47: 1–8 (1974).

    PubMed  CAS  Google Scholar 

  • Dube, W.J.; Goldsmith, R.S.; Arnaud, S.B. and Arnaud, CD.: Hyperparathyroidism secondary to long-term therapy of Paget’s disease of bone with calcitonin; in Talmage and Munson (Eds) Calcium. Parathyroid hormone and the Calcitonins, pp. 113–115 (Excerpta Medica, Amsterdam 1972).

    Google Scholar 

  • Epstein, S. and Owen, G.: Paget’s disease of bone (osteitis deformans) treated with human synthetic calcitonin. South African Medical Journal 51: 133–137 (1977).

    PubMed  CAS  Google Scholar 

  • Evans, G.A. and Slee, G.A.: Calcitonin for multiple fractures in Paget’s disease. British Medical Journal 1: 357 (1977).

    PubMed  CAS  Google Scholar 

  • Evans, I.M.A.: Human calcitonin in the treatment of Paget’s disease; long term trial; in MacIntyre (Ed.) Human Calcitonin and Paget’s Disease, pp. 111–123 (Hans Huber, Berne 1977).

    Google Scholar 

  • Evans, I.M.A.; Banks, L.; Doyle, F.H.; Joplin, G.F.; Pennock, J. et al.: Paget’s disease of bone — the effect of stopping long term human calcitonin and recommendations for future treatment. Metabolic Bone Disease and Related Research 2: 87–92 (1980).

    Google Scholar 

  • Fast, D.K.; Felix, R.; Dowse, C; Neuman, W.F. and Fleisch, H.: The effects of diphosphonates on the growth and glycolysis of connective-tissue cells in culture. Biochem. J. 172: 97 (1978).

    PubMed  CAS  Google Scholar 

  • Finerman, G.A.M.; Gonick, H.C; Smith, R.K. and Mayfield, J.M.: Diphosphonate treatment of Paget’s disease. Journal of Clinical Orthopaedics and Related Research 120: 115–124 (1976).

    Google Scholar 

  • Fleisch, H.: Bisphosphonates; mechanisms of action and clinical applications; in Peck (Ed.) Bone and Mineral Research Annual 1, pp. 319–357 (Excerpta Medica, Amsterdam 1983).

    CAS  Google Scholar 

  • Fleisch, H.; Russell, R.G.G. and Straumann, T.: Effect of pryophosphate on hydroxyapatite and its implications in calcium homeostasis. Nature 212: 901–903 (1966).

    CAS  Google Scholar 

  • Foster, G.V.; MacIntyre, I. and Pearse, A.G.E.: Calcitonin production and the mitochondrion rich cells of the dog thyroid. Nature 203: 1029–1030 (1964).

    PubMed  CAS  Google Scholar 

  • Franck, W.A.; Bress, N.M.; Singer, F.R. and Krane, S.M.: Rheumatic manifestations of Paget’s disease of bone. American Journal of Medicine 56: 592–603 (1974).

    PubMed  CAS  Google Scholar 

  • Friedman, J. and Raisz, L.G.: Thyrocalcitonin, inhibitor of bone resorption in tissue culture. Science 150: 1465–1467 (1965).

    PubMed  CAS  Google Scholar 

  • Friedman, P.; Sklaver, N. and Klawans, H.L.: Neurological manifestations of Paget’s diseases of the skull. Disease of the Nervous System 32: 809–817 (1971).

    CAS  Google Scholar 

  • Frijlink, W.B.; Bijvoet, O.L.M.; TeVelde, J. and Heynen, G.: Treatment of Paget’s disease with (3-amino-1-hydroxypropylidene)-1,1-Diphosphonate (APD). Lancet 1: 799–803 (1979).

    PubMed  CAS  Google Scholar 

  • Fromm, G.; Schajowicz, E. and Mautalen, CA.: Disodium ethanel-hydroxy-l,l-diphosphonate(EHDP) in Paget’s disease. Lancet 2: 666 (1975).

    PubMed  CAS  Google Scholar 

  • Gasser, A.B.; Morgan, D.B.; Fleisch, H.A. and Richell, L.J.: The influence of two diphosphonates on calcium metabolism in the rat. Clinical Science 43: 31–45 (1972).

    PubMed  CAS  Google Scholar 

  • Goldfield, E.B.; Braiker, B.M.; Prendergast, J.J. and Kolb, F.O.: Synthetic salmon calcitonin: Treatment of Paget’s disease and osteoporosis imperfects. Journal of the American Medical Association 221: 1127–1129 (1972).

    PubMed  CAS  Google Scholar 

  • Grimaldi, P.M.G.B.; Mohamedally, S.M. and Woodhouse, N.J.Y.: Deafness in Paget’s disease: Effect of salmon calcitonin. British Medical Journal 2: 726–727 (1975).

    PubMed  CAS  Google Scholar 

  • Grubb, S.A.; Markham, T.C and Talmage, R.V.: Effect of calcitonin infusion on plasma concentrations of recently administered radiocalcium. Calcified Tissue Research 24: 201–208 (1977).

    PubMed  CAS  Google Scholar 

  • Grunstein, H.; Clifton-Bligh, O. and Posen, S.: Pagets disease of bone: experiences with 100 patients treated with salmon calcitonin. Medical Journal of Australia 2: 278–280 (1981).

    PubMed  CAS  Google Scholar 

  • Guncaga, L.; Lauffenburger, T.; Lentner, C; Dambacher, M.A. and Haas, H.G.: Diphosphonate treatment of Paget’s disease of bone. Hormone and Metabolic Research 6: 62–69 (1974).

    PubMed  CAS  Google Scholar 

  • Guttman, S.: Chemistry and structure — activity relationship of natural and synthetic calcitonins; in Pecile (Ed.) Calcitonin 1980: Chemistry, Physiology, Pharmacology and Clinical Aspects pp. 11–24 (Excerpta Medica, Amsterdam 1981).

    Google Scholar 

  • Haddad, J.G. and Caldwell, J.G.: Calcitonin resistance: Clinical and immunologic studies in subjects with Paget’s disease of bone treated with porcine and salmon calcitonin. Journal of Clinical Investigation 51: 3133–3141 (1972).

    PubMed  Google Scholar 

  • Hadjipavlou, A.G.; Tsoukas, G.M.; Siller, T.N.; Danias, S. and Greenwood F.: Combination drug therapy in treatment of Paget’s disease of bone. Journal of Bone and Joint Surgery 59A: 1045–1051 (1977).

    Google Scholar 

  • Hamdy, R.C.: Paget’s Disease of Bone, pp. 1–3 (Praeger Scientific, New York (1981)

    Google Scholar 

  • Hamilton, C.R.: Effect of synthetic salmon calcitonin in patients with Paget’s disease of bone. American Journal of Medicine 56: 315–322 (1974).

    PubMed  Google Scholar 

  • Harell, A.; Binderman, I. and Rodan, G.A.: The effect of calcium concentration on calcium uptake by bone cells treated with thyrocalcitonin (TCT) hormone. Endocrinology 92: 550–555 (1973).

    PubMed  CAS  Google Scholar 

  • Haymovitis, A.; Zluizek, V.; Ling, A.S.C.; Hobitz, J. and Fotino, M.: Studies on short term therapy with human calcitonin and ultrastructural, immunological and genetic observations on the aetiology of Paget’s disease; in MacIntyre (Ed.) Human Calcitonin and Paget’s Disease, pp. 138–154 (H. Huber, Bern 1977).

    Google Scholar 

  • Herzberg, L. and Bayliss, E.: Spinal cord syndrome due to non-compressive Pagets disease of bone: A spinal artery steal phenomenon reversible with calcitonin. Lancet 2: 13–15 (1980).

    PubMed  CAS  Google Scholar 

  • Hill, L.F.; Lumb, G.A.; Mawer, E.B. and Stanbury, S.W.: Indirect inhibition of the biosynthesis of 1,25-dihydroxycholecalciferol in rats treated with a diphosphonate. Clinical Science 44: 335–347 (1973).

    PubMed  CAS  Google Scholar 

  • Holtrop, M.E.; Raisz, L.G. and Simmons, H.A.: The effects of parathyroid hormone, colchicine and calcitonin on the ultrastructure and activity of osteoclasts in organ culture. Journal of Cell Biology 60: 346–355 (1974).

    PubMed  CAS  Google Scholar 

  • Hosking, D.J.: Calcitonin and diphosphonate in the treatment of Paget’s disease of bone. Metabolic Bone Disease and Related Research 3: 317–326 (1981a).

    CAS  Google Scholar 

  • Hosking, D.J.: Clinical significance of calcitonin antibodies; in Pecile (Ed.) Calcitonin 1980, pp. 365–377 (Excerpta Medica, Amsterdam 1981b).

    Google Scholar 

  • Hosking, D.J.; Bijvoet, O.L.M.; Van Aken, J. and Will, E.J.: Paget’s bone disease treated with diphosphonate and calcitonin. Lancet 1: 615–617 (1976).

    PubMed  CAS  Google Scholar 

  • Hosking, D.J.; Vennart, W. and Huddlestone, L.B.: Bone turnover in Paget’s disease. Biochemical and kinetic measurements during salmon calcitonin therapy. Calcified Tissue International 31: 471–476 (1981).

    Google Scholar 

  • Johnston, C.C.; Khairi, M.R.A. and Meunier, P.J.: Use of etidronate (EHDP) in Paget’s disease of bone. Arthritis and Rheumatism 23: 1172–1176 (1980).

    PubMed  Google Scholar 

  • Jung, A.; Merillod, B.; Schenk, R.; Courvoisier, B.; Burckhardt, P.; Epiney, J. and Fleisch, H.: Traitement de 10 cas symptomatiques de maladie de Paget par l’etidronte (EHDP). Schweiz. Med. Woch. 106: 1667–1673 (1976).

    CAS  Google Scholar 

  • Kanis, J.A.; Fitzpatrick, K. and Strong, J. A.: Treatment of Paget’s disease with porcine calcitonin. Clinical and metabolic responses. British Medical Journal 44: 399–413 (1975).

    CAS  Google Scholar 

  • Kanis, J.A.; Horn, D.B.; Scott, R.D.M. and Strong J.A.: Treatment of Paget’s disease of bone with synthetic salmon calcitonin. British Medical Journal 3: 727–731 (1974).

    PubMed  CAS  Google Scholar 

  • Kantrowitz, F.G.; Byrne, M.H.; Schiller, A.L. and Krane, S.M.: Clinical and biochemical effects of diphosphonates in Paget’s disease of bone. Arthritis and Rheumatism 18: 407 (1975).

    Google Scholar 

  • Khairi, M.R.A.; Altman, R.D.; DeRosa, G.P.; Zimmerman, J. et al.: Sodium etidronate in the treatment of Paget’s disease of bone. A study of long term results. Annals of Internal Medicine 87: 656–663 (1977).

    PubMed  CAS  Google Scholar 

  • Khairi, MRA., Johnston, C.C.; Altman, R.D.; Wellman, H.N.; Serafani, A.N. and Sankey, R.R.: Treatment of Paget’s disease of bone (osteitis deformans). Results of one year study with sodium etidronate. Journal of the American Medical Association 230: 562–567 (1974)

    PubMed  CAS  Google Scholar 

  • Martin, T.J.: Treatment of Paget’s disease with calcitonins. Australian and New Zealand Journal of Medicine 9: 36–43 (1979).

    PubMed  CAS  Google Scholar 

  • Martin, T.J.; Jerums, G.; Melick, R.A.; Xipell, J.M. and Arnott, R.: Clinical, biochemical and histological observations on the effect of porcine calcitonin in Pagets disease of bone. Australian and New Zealand Journal of Medicine 7: 36–43 (1977).

    PubMed  CAS  Google Scholar 

  • Marx, S.J.; Woodward, C.J. and Aurbach, G.D.: Calcitonin receptors of kidney and bone. Science 178: 999–1000 (1972).

    PubMed  CAS  Google Scholar 

  • Mathews, J.L.; Martin, J.H.; Collins, E.J.; Kennedy, J.W. and Powell, E.L.: Immediate changes in the ultrastructure of bone cells following thyrocalcitonin administration; in Talmage and Munson (Eds.) Calcium, Parathyroid Hormone and the Calcitonins. International Congress Series 243, pp. 375–382 (Excerpta Medica, Amsterdam 1972).

    Google Scholar 

  • Melick, R.A.; Ebeling, P. and Hjorth, R.J.: Improvement in paraplegia and vertebral Paget’s disease treated with calcitonin. British Medical Journal 1: 626–628 (1976).

    Google Scholar 

  • Menzies, M.A.; Greengerg, P.B. and Joplin, G.F.: Otological studies in patients with deafness due to Paget’s disease before and after treatment with synthetic human calcitonin. Acta Otolaryngologica 79: 378–383 (1975).

    CAS  Google Scholar 

  • Meunier, P.: Paget’s disease of bone. Quantitative histology, histopathogenesis and therapeutic prospects. Lyon Médical 233: 839–853 (1975).

    Google Scholar 

  • Meunier, P.; Chapuy, M.C.; Alexandre, C; Bressot, C; Edouard, C. et al.: Effects of disodium dichloromethylene diphosphonate on Paget’s disease of bone. Lancet 2: 489–492 (1979).

    PubMed  CAS  Google Scholar 

  • Meunier, P.; Chapuy, M.C.; Courpron, P.; Vignon, E.; Edouard, C. and Bernard, J.: Effects cliniques, biologiques et histologiques de l’ethane-1-hydroxy 1, 1 diphosphonate (EHDP) dans la maladie de Paget. Revue du Rheumatisme 42: 699–705 (1975).

    CAS  Google Scholar 

  • Meyers, M.H. and Singer, F.R.: Osteotomy for tibia vara in Paget’s disease under cover of calcitonin. Journal of Bone and Joint Surgery 60A: 810–814 (1978).

    Google Scholar 

  • Michael, W.R.; King, W.R. and Wakim, J.M.: Metabolism of disodium ethane-1-hydroxy-1, 1-diphosphonate (disodium etidronate) in the rat, rabbit, dog and monkey. Toxicology and Applied Pharmacology 21: 503–515 (1972).

    PubMed  CAS  Google Scholar 

  • Moffatt, W.H.; Morrow, J.D. and Simpson, N.: Effect of calcitonin therapy in deafness associated with Paget’s disease of bone. British Medical Journal 4: 203 (1974).

    PubMed  CAS  Google Scholar 

  • Murphy, W.A.; Whyte, M.P. and Haddad, J.G.: Paget’s bone disease: Radiologic documentation of healing with human calcitonin therapy. Radiology 136: 1–4 (1980).

    PubMed  CAS  Google Scholar 

  • Nagant de Deuxchaisnes, C. and Krane, S.M.: Paget’s disease of bone. Clinical and metabolic observations. Medicine (Baltimore) 43: 233–266 (1964).

    CAS  Google Scholar 

  • Nagant de Deuxchaisnes, C; Rombouts-Lindermans, C; Huaux, J.P.; Malgham, J. and Maldague, B.: Roentgenologic evaluation of the efficacy of calcitonin in Paget’s disease of bone; in MacIntyre and Szelke (Eds) Molecular Endocrinology, pp. 213–233 (Elsevier/North Holland Biomedical Press, Amsterdam 1977).

    Google Scholar 

  • Nagant de Deuxchaisnes, C; Rombouts-Lindemans, C; Huaux, J.P.; Devogelaer, J.P.; Malgham, J. and Maldague, B.: Roentgenologic evaluation of the action of the diphosphonate EHDP and of combined therapy (EHDP and calcitonin) in Pagets disease of bone; in MacIntyre and Szelke (Eds) Molecular Endocrinology, pp. 405–433 (Elsevier/North Holland Biomedical Press, Amsterdam 1979).

    Google Scholar 

  • Newsome, F.E.; O’Dor, R.K.; Parkes, CO. and Copp, D.H.: A study of stability of calcitonin biological activity. Endocrinology 92: 1102–1106 (1973).

    PubMed  CAS  Google Scholar 

  • Plehwe, W.E.; Hudson, J.; Clifton-Bligh, P. and Posen, S.: Porcine calcitonin in the treatment of Paget’s disease of bone. Medical Journal of Australia 1: 577–581 (1977).

    PubMed  CAS  Google Scholar 

  • Rasmusscn, H. and Bordier, P.: Primary disorders of bone cell function: in The Physiological and Cellular Basis of Metabolic Bone Disease, pp. 292–303 (Williams and Wilkins, Baltimore 1974).

    Google Scholar 

  • Rebel, A.; Basle, M.; Minard, M.F. and Malakani, K.: Actions de la calcitonine sur les osteoclasts de la maladie de Paget au cours d’un traitement de longue durée. Pathologie Biologie 25: 611–616 (1977).

    PubMed  CAS  Google Scholar 

  • Rebel, A.; Malkani, K.; Basle, M. and Bregeon, C: Osteoclast ultrastructure in Paget’s disease. Calcified Tissue Research 20: 187–199 (1976).

    Google Scholar 

  • Recker, R.R. and Saville, P.D.: Intestinal absorption of disodium ethane-1-hydroxy-1, 1-diphosphonate (disodium etidronate) using a deconvolution technique. Toxicology and Applied Pharmacology 24: 580–589 (1973).

    PubMed  CAS  Google Scholar 

  • Reiner, M. Jung, A.; Seiler, A.; Schenk, R. and Fleisch, H.: Le traitement de la maladie de Paget par les diphosphonates. Schweiz. Med. Woch. 105: 1701–1703 (1975).

    CAS  Google Scholar 

  • Reitsma, P.H.; Bijvoet, O.L.M.; Verlinden-Ooms, H. and Van der Wee-Pals, L.J.A.: Kinetic studies of bone and mineral metabolism during treatment with (3-amino-l-hydroxypropylidene)-1,1-bisphosphonate (ADP) in rats. Calcified Tissue International 32: 145–147 1980).

    PubMed  CAS  Google Scholar 

  • Riggs, L. and Jowsey, J.: Treatment of Paget’s disease with fluoride. Seminars in Drug Treatment 2: 65–75 (1972).

    PubMed  CAS  Google Scholar 

  • Russell, R.G.G.; Smith, R.; Preston, C; Walton, R.J. and Woods, CG.: Diphosphonates in Paget’s disease. Lancet 1: 894–898 (1974).

    PubMed  CAS  Google Scholar 

  • Ryan, W.G.: Treatment of Paget’s disease of bone with mithramycin. Clinical Orthopaedics and Related Research 127: 106–110 (1977).

    PubMed  Google Scholar 

  • Schenk, R., Merz, W.A.; Muhlbauer, R.; Russel, R.G.G. and Fleisch, FL: Effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) and dichloromethylene diphosphonate (Cl2MDP) on the calcification and resorption of cartilage and bone in the tibial epiphysis and metaphysis of rats. Calcified Tissue Research 11: 196–214 (1973).

    PubMed  CAS  Google Scholar 

  • Shai, F.; Baker, R.K. and Wallach, S.: The clinical and metabolic effects of porcine calcitonin on Pagets disease of bone. Journal of Clinical Investigation 50: 1927–1940 (1971).

    PubMed  CAS  Google Scholar 

  • Silva, O.L. and Becker, K.L.: Immunoreactive calcitonin in extrathyroidial tissues; in Pecile (Ed.) Calcitonin 1980. Chemistry, Physiology, Pharmacology and Clinical Aspects, pp. 144–153 (Excerpta Medica, Amsterdam 1981).

    Google Scholar 

  • Singer, F.R.; Aldred, J.P.; Neer, R.M.; Krane, S.M.; Potts Jr, J.T. and Bloch, K.J.: An evaluation of antibodies and clinical resistance to salmon calcitonin. Journal of Clinical Investigation 51: 2331–2338 (1972).

    PubMed  CAS  Google Scholar 

  • Singer, F.R.; Fredericks, R.S. and Minkin, C: Salmon calcitonin therapy for Paget’s disease of bone. The problem of acquired clinical resistance. Arthritis and Rhematism 23: 1148–1154 (1980).

    CAS  Google Scholar 

  • Singer, F.R.; Rude, R.K. and Mills, B.G.: Studies of the treatment and aetiology of Paget’s disease of bone; in MacIntyre, (Ed.) Human Calcitonin and Paget’s Disease, pp. 93–110 (H. Huber, Bern 1977).

    Google Scholar 

  • Singer F.R.; Rude, R.K. and Mills, B.G.: Paget’s disease of bone; in Avioli and Krane (Eds) Metabolic Bone Disease, pp. 489–575 (Academic Press, New York 1978).

    Google Scholar 

  • Siris, E.S.; Canfield, R.E.; Jacobs, T.P. and Baquiran, D.C.: Long term therapy of Paget’s disease of bone with EHDP. Arthritis and Rheumatism 23: 1177–1184 (1980).

    PubMed  CAS  Google Scholar 

  • Siris, E.S.; Canfield, R.E.; Jacobs, T.P.; Stoddart, K.E. and Spector, P.J.: Clinical and biochemical effects of EHDP in Paget’s disease of bone: Patterns of response to initial treatment and to long term therapy. Metabolic Bone Disease and Related Research 3: 301–308 (1981).

    CAS  Google Scholar 

  • Stein, L; Shapiro, B.; Ostrum, B. and Beller, M.: Evaluation of sodium etidronate in the treatment of Paget’s disease of bone. Clinical Orthopaedics and Related Research 122: 347–358 (1977).

    PubMed  Google Scholar 

  • Stevens, J.: Orthopaedic aspects of Paget’s disease. Metabolic Bone Disease and Related Research 3: 271–278 (1981).

    CAS  Google Scholar 

  • Sturtridge, W.C.; Harrison, J.E. and Wilson, D.R.: Long term treatment of Paget’s disease of bone with salmon calcitonin. Canadian Medical Association Journal 117: 1031–1034(1977).

    PubMed  CAS  Google Scholar 

  • Talmage, R.V. and Anderson, J.J.B.: Parathyroid hormone effects in rats treated with diphosphonates. Science 183: 661–663 (1974).

    PubMed  CAS  Google Scholar 

  • Talmage, R.V.; Cooper, C.W. and Toverud, S.U.: The physiological significance of calcitonin; in Peck (Ed.) Bone and Mineral Research Annual 1, pp. 74–143 (Excerpta Medica, Amsterdam 1983).

    CAS  Google Scholar 

  • Talmage, R.V.; Hirsch, P.F. and Van der Weil, C.J.: Calcitonin, feeding and calcium conservation; in Pecile (Ed.) Calcitonin 1980. Chemistry, Physiology, Pharmacology and Clinical Aspects, pp. 96–109 (Excerpta Medica, Amsterdam 1981).

    Google Scholar 

  • Tashjian, A.H.; Wright, D.R.; Ivey, J.L. and Pont, B.: Calcitonin binding sites in bone: Relationships to biological response and escape. Recent Progress in Hormone Research 34: 285–334 (1978).

    PubMed  CAS  Google Scholar 

  • Treschsel, U.; Bonjour, J.-P. and Fleisch, H.: Regulation of the metabolism of 25-hydroxyvitamin D3 in primary cultures of chick kidney cells. Journal of Clinical Investigation 64: 206–217 (1979).

    Google Scholar 

  • Treschsel, U.; Schenk, R.; Bonjour, J.-P.; Russell, R.G.G. and Fleisch, H.: Relation between bone mineralization, Ca absorption, and plasma Ca in phosphonate-treated rats, American Journal of Physiology 232: E298–E305 (1977).

    Google Scholar 

  • Walton, R.J.; Russel, R.G.G. and Smith, R.: Changes in the renal and extrarenal handling of phosphate induced by disodium etidronate (EHDP) in man. Clinical Science and Molecular Medicine 49: 45–56 (1975).

    PubMed  CAS  Google Scholar 

  • Warshawsky, H.; Goltzman, D.; Rouleau, M.F. and Bergeron, J.J.M.; Direct in-vivo demonstration by radioautography of specific binding sites for calcitonin in skeletal and renal tissues of the rat. Journal of Cell Biology 85: 682–694 (1980).

    PubMed  CAS  Google Scholar 

  • Wener, J.A.; Gorton, S.J. and Raisz, L.G.: Escape from inhibition of resorption in cultures of foetal bone treated with calcitonin and parathyroid hormone. Endocrinology 90: 752–759 (1972).

    PubMed  CAS  Google Scholar 

  • Williams, CP.; Meachim, G. and Taylor, W.H.: Effect of calcitonin treatment on osteoclast counts in Pagets disease of bone. Journal of Clinical Pathology 31: 1212–1217 (1978).

    PubMed  CAS  Google Scholar 

  • Woodhouse, N.J.Y.: Paget’s disease of bone. Journal of Clinical Endocrinology and Metabolism 1: 125–141 (1972).

    Google Scholar 

  • Woodhouse, N.J.Y.; Bordier, P.; Fisher, M.; Joplin, G.F.; Reiner, M. et al.: Human calcitonin in the treatment of Paget’s disease. Lancet 1: 1139–1143 (1971).

    PubMed  CAS  Google Scholar 

  • Woodhouse, N.J.Y.; Crosbie, W.A. and Mohamedally, S.M.: Cardiac output in Paget’s disease: Response to long term salmon calcitonin therapy. British Medical Journal 4: 686 (1975).

    PubMed  CAS  Google Scholar 

  • Woodhouse, N.J.Y.; Joplin, G.F.; MacIntyre, I. and Doyle, F.H.: Radiological regression in Paget’s disease treated by human calcitonin. Lancet 2: 992–994 (1972).

    PubMed  CAS  Google Scholar 

  • Woodhouse, N.J.Y.; Mohamedally, S.M.; Saed-Nejad, L.F. and Martin, T.J.: Development and significance of antibodies to salmon calcitonin in patients with Paget’s disease on long term treatment. British Medical Journal 2: 927–929 (1977).

    PubMed  CAS  Google Scholar 

  • Wooton, R.; Reeve, J.; Spellacy, E. and Tellez-Yudilevich, M.: Skeletal blood flow in Paget’s disease of bone and its response to calcitonin therapy. Clinical Science and Molecular Medicine 54: 69–74 (1978).

    Google Scholar 

  • Zeigler, R.; Holz, G.; Rave, F.; Minne, H. and Delling, G.: Therapeutics studies with human calcitonin; in MacIntyre (Ed.) Human Calcitonin and Paget’s Disease, pp. 167–173 (H. Huber, Bern 1977).

    Google Scholar 

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Hosking, D.J. Paget’s Disease of Bone. Drugs 30, 156–173 (1985). https://doi.org/10.2165/00003495-198530020-00004

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