Objectives: To test the effects of 200 IU/day of a nasal spray of salmon calcitonin in modulating the increased bone tissue metabolism observed in hemiplegic patients.
Design: A two-year, prospective, randomized, double-blind, placebo-controlled study.
Patients: Thirty-four patients with hemiplegia due to a cerebrovascular accident were included in the study during the first month after onset of hemiplegia after giving their informed consent. All patients followed a suitably planned course of active rehabilitation according to Bobath. They were randomly allocated to either the calcitonin or the placebo group but all of them received a daily oral calcium supplementation of 1000 mg.
Results: Biochemical markers of bone formation, serum total alkaline phosphatase, osteocalcin and type I procollagen did not vary during the two years of follow-up. Cross-linked carboxy-terminal telopeptide of type I collagen, a biochemical marker of bone resorption, was elevated initially after stroke and then decreased significantly (p <0.001), stabilizing as of month 12. Urinary calcium/creatinine and total hydroxyproline/creatinine ratios presented with similar profiles. The serum levels of the type III procollagen, a marker of connective tissue metabolism, were also elevated upon entry and decreased thereafter. No significant difference could be found between the calcitonin-treated and the placebo group for any of the biochemical markers at any time point.
Conclusion: This prospective study demonstrated that biochemical markers of bone and connective tissue metabolism were elevated shortly after the occurrence of stroke and then gradually decreased during the first two years after injury. The daily administration of 200 IU of intranasal calcitonin did not influence the levels of these markers.
Get full access to this article
View all access options for this article.
References
1.
Peszczynski M. The fractured hip in hemiplegic patients. Geriatrics1957; 12: 687–690.
2.
Ramnemark A, Nyberg L, Borssén B, Olsson T, Gustafson Y. Fractures after stroke. Osteoporos Int1998; 8: 92–95.
3.
Takamoto S, Masuyama T, Nakajima M et al. Alterations of bone mineral density of the femurs in hemiplegia. Calcif Tissue Int1995; 56: 259–262.
4.
Del Puente A, Pappone N, Mandes MG, Mantova D, Scarpa R, Oriente P. Determinants of bone mineral density in immobilization: a study on hemiplegic patients. Osteoporos Int1996; 6: 50–54.
5.
Tanaka N, Sonoda S, Kondo K, Chino N. Reproducibility of dual-energy X-ray absorptiometry in the upper extremities in stroke patients. Disabil Rehabil1997; 19: 523–527.
6.
Mayo NE, Korner-Bitensky N, Becker R et al. Predicting falls among patients in a rehabilitation hospital. Am J Phys Med Rehabil1989; 68: 139–146.
7.
Nyberg L, Gustafson Y. Patients falls in stroke rehabilitation: a challenge to rehabilitation strategies. Stroke1995; 26: 838–842.
8.
Forster A, Young J. Incidence and consequences of falls due to stroke: a systematic inquiry. BMJ1995; 311: 83–86.
9.
Panin N, Gorday WJ, Paul BJ. Osteoporosis in hemiplegia. Stroke1971; 2: 41–47.
10.
Naftchi NE, Viau AT, Marshall CH, Davis S, Loman EW. Bone mineralisation in the distal forearm of hemiplegic patients. Arch Phys Med Rehabil1975; 56: 487–492.
11.
Prince RL, Price RI, Ho S. Forearm bone loss in hemiplegia: a model for the study of immobilization osteoporosis. J Bone Min Res1988; 3: 305–310.
12.
Singh A, Shah S, Kaplan P. Appendicular and spinal bone mineral content in early stroke. In: Dequeker J, Geusens P, Wahner HW eds. Bone mineral measurements by photon absorptiometry: methodological problems. Leuven: Leuven University Press, 1988: 344–346.
13.
Iversen E, Hassager C, Christiansen C. The effect of hemiplegia on bone mass and soft tissue body composition. Acta Neurol Scand1989; 79: 155–159.
14.
Hamdy RC, Moore SW, Cancellaro VA, Harvill LM. Long-term effects of strokes on bone mass. Am J Phys Med Rehabil1995; 74: 351–356.
15.
Van Ouwenaller C, Uebelhart D, Chantraine A. Bone metabolism in hemiplegic patients. Scand J Rehabil Med1989; 21: 165–170.
16.
Copp DH, Cameron EC, Cheney BA, Davidson AGF, Henze KG. Evidence for calcitonin, a new hormone from the parathyroid that lowers blood calcium. Endocrinology1962; 70: 638–649.
17.
Chambers TJ, Magnus CJ. Calcitonin alters behaviour of isolated osteoclasts. J Pathol (Lond)1982; 136: 27–39.
18.
Van der Wiel HE, Lips P et al. Intranasal calcitonin suppresses increased bone resorption during short-term immobilization: a double-blind study of the effects of intranasal calcitonin on biochemical parameters of bone turnover. J Bone Min Res1993; 8: 1459–1465.
19.
Reginster JY, Denis D, Deroisy R et al. Long-term (3 years) prevention of trabecular postmenopausal bone loss with low-dose intermittent nasal salmon calcitonin. J Bone Min Res1994; 9: 69–73.
20.
Reginster JY, Meurmans L, Deroisy R, Jupsin I, Biquet I, Albert A, Franchimont P. A 5-years controlled randomized study of prevention of postmenopausal trabecular bone loss with salmon calcitonin and calcium. Eur J Clin Invest1994; 24: 565–569.
21.
Barbezat S. Etude prospective randomisée et en double aveugle sur l'efficacité d'un traitement de calcitonine en spray nasal chez des hémiplégiques. MD thesis, Faculty of Medicine, University of Geneva, 1993.
22.
Brixen K, Nielsen HK, Eriksen EF, Charles P, Mosekilde L. Efficacy of wheat germ lectinprecipitated alkaline phosphatase in serum as an estimator of bone mineralization rate: comparison to serum total alkaline phosphatase and serum bone Gla-protein. Calcif Tissue Int1989; 44: 93–98.
23.
Garnero P, Grimaux M, Demiaux B, Preaudat C, Seguin P, Delmas PD. Measurement of serum osteocalcin with a human-specific two-site immunoradiometric assay. J Bone Min Res1992; 7: 1389–1398.
24.
Melkko J, Niemi S, Risteli L, Risteli J. Radioimmunoassay of the carboxyterminal propeptide of human type I procollagen. Clin Chem1990; 36: 1328–1332.
25.
Risteli J, Elooma I, Niemi S, Novamo A, Risteli L. Radioimmunoassay for the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen: a new serum marker of bone collagen degradation. Clin Chem1993; 39: 635–640.
26.
Kivirikko KI, Laitinen OI, Prockop DJ. Modifications of a specific assay for hydroxyproline in urine. Anal Biochem1967; 19: 249–255.
27.
Risteli L, Risteli J. Non invasive methods for detection of organ fibrosis. In: Rojkind M ed. Connective tissue in health and disease, Volume 1. Boca Raton: CRC Press, 1989.
28.
Katz IA, Epstein S. Post transplantation bone disease. J Bone Min Res1992; 7: 123–126.
29.
Uebelhart D, Hartmann D, Vuagnat H, Castanier M, Hachen HJ, Chantraine A. Early modifications of biochemical markers of bone metabolism in spinal cord injury patients: a preliminary study. Scand J Rehabil Med1994; 26: 197–202.
30.
Kanis JA, Delmas P, Burckhardt P, Cooper C, Torgerson D. Guidelines for diagnosis and management of osteoporosis. Osteoporos Int1997; 7: 390–406.
31.
Chambers TJ, Moore A. The sensitivity of isolated osteoclasts to morphological transformation by calcitonin. J Clin Endocrinol Metab1983; 57: 819–824.
32.
Abbiati G, Arrigoni M, Grignani S, Longoni A, Bartucci F, Castiglioni C. Effect of salmon calcitonin on deoxy-pyridinoline (Dpr) urinary excretion in healthy volunteers. Calcif Tissue Int1994; 55: 346–348.
33.
Kanis JA, Johnell O, Gullberg B et al. Evidence for efficacy of drugs affecting bone metabolism in preventing hip fracture. BMJ1992; 305: 1124–1128.
34.
Cardona JM, Pastor E. Calcitonin versus etidronate for the treatment of postamenopausal osteoporosis: a meta-analysis of published clinical trials. Osteopororis Int1997; 7: 165–174.
35.
Plosker GL, McTavish D. Intranasal salmon calcitonin: a review of its pharmacological properties and role in the management of postmenopausal osteoporosis. Drugs Aging1996; 8: 378–400.
36.
Overgaard K. Effect of intranasal salmon calcitonin therapy on bone mass and bone turnover in early postmenopausal women: a dose-response study. Calcif Tissue Int1994; 55: 82–86.
37.
Munk Nielsen N, Von der Recke P, Hansen MA, Overgaard K, Christiansen C. Estimation of the effect of salmon calcitonin in established osteoporosis by biochemical markers. Calcif Tissue Int1994; 55: 8–11.
38.
Devogelaer JP, Azria M, Attinger M, Abbiati G, Castiglioni C, Nagant de Deuxchaisnes C. Comparison of the acute biological action of injectable salmon calcitonin and an injectable and oral calcitonin analogue. Calcif Tissue Int1994; 55: 71–73.
39.
Combe B, Cohen C, Aubin F. Equivalence of nasal spray and subcutaneous formulations of salmon calcitonin. Calcif Tissue Int1997; 61: 10–15.
40.
Ongphiphadhanakul B, Piaseu N, Chailurkit L, Rajatanavin R. Suppression of bone resorption in early postmenopausal women by intranasal salmon calcitonin in relation to dosage and basal bone turnover. Calcif Tissue Int1998; 62: 379–382.
41.
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 Med1995; 98: 452–458.
42.
Deftos LJ, Nolan JJ, Seely BL et al. Intrapulmonary drug delivery of salmon calcitonin. Calcif Tissue Int1997; 61: 345–347.
43.
Uebelhart D, Chantraine A, Demiaux-Domenech B. Use of biochemical markers to assess bone metabolism: a critical review for the rehabilitation medicine physician. J Rehabil Sci1995; 8: 34–38.
