[en] We sought to assess efficacy and safety of a new oral formulation (tablet) of tiludronate in Paget's disease of bone. We studied 128 patients with Paget's disease in an open-label uncontrolled trial. Patients received a daily dose of 400 mg oral tiludronate (two tablets). Treatment was for 6 months. Serum alkaline phosphatase activity (SAP) and fasting urinary excretion of hydroxyproline/creatine (OH/Cr) were measured every 3 months, as were biochemical parameters reflecting renal, hepatic, and hematologic functions. Analgesic efficacy was self-evaluated from a visual analog scale (VAS). Statistical analysis revealed a significant reduction from baseline in SAP and OH/Cr levels, as well as VAS scores. In the whole population with evaluation under treatment, there was a reduction in initial SAP activity after 3 months (47.2 +/- 2.2%, mean +/- SEM) and 6 months (58.3 +/- 2.3%). In the population with SAP levels above twice the upper limit at inclusion and with evaluation at month 3 and month 6 (n = 96), the reduction in SAP levels was 49.3 +/- 2.4% after 3 months and of 59.5 +/- 2.6% after 6 months (ANOVA time effect, p = 0.0001). Aside from mild gastrointestinal disturbances, as experienced with other oral bisphosphonates, clinical tolerance was good. Exhaustive biochemical investigation failed to reveal significant toxicity of tiludronate tablets at the dose of 400 mg/day. The dose of 400 mg daily of this new formulation appears to be a satisfactory tiludronate regimen for the treatment of Paget's disease of bone.
Disciplines :
Rheumatology
Author, co-author :
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Treves, R.
Renier, J. C.
Amor, B.
Sany, J.
Ethgen, Dominique ; Université de Liège - ULiège > Epidémiologie et santé publique
Picot, C.
Franchimont, P.
Language :
English
Title :
Efficacy and Tolerability of a New Formulation of Oral Tiludronate (Tablet) in the Treatment of Paget's Disease of Bone
Publication date :
May 1994
Journal title :
Journal of Bone and Mineral Research
ISSN :
0884-0431
eISSN :
1523-4681
Publisher :
Wiley-Blackwell, Washington, United States - District of Columbia
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Meunier PJ, Coindre JM, Edouard CM, Arlot MD (1980) Bone histomorphometry in Paget's disease. Quantitative and dynamic analysis of pagetic and non‐pagetic bone tissues. Arthitis Rheum. 23:1095-1103.
Mills BG, Singer FR (1976) Nuclear inclusions in Paget's disease of bone. Science 194:201-202.
Rebel A, Malkani K, Basle M, Bregean C (1976) Osteoclasts ultrastructure in Paget's disease. Calcif Tissue Int 20:187-189.
Fleisch H, Russell RG, Francis MD (1969) Diphosphonates inhibit hydroxyapatite dissolution in vitro and bone resorption in culture tissue and in vivo. Science 165:1261-1264.
Vignery A, Baron R (1980) Comparative effects of APD and Cl2MDP on bone in the rat: In vivo and in vitro studies. Metab Bone Dis 2:381-387.
Kanis JA, Gray RES (1987) Long term follow‐up observations on treatment of Paget's disease of bone. Clin Orthop. 217:99-125.
Fleisch H (1987) Experimental basis for the use of bisphosphonates in Paget's disease of bone. Clin Orthop 217:72-78.
Emonts‐Alt X, Breliere JC, Roncucci R (1985) Effects of 1‐hydroxyethylidene‐1, 1‐bisphosphonate and (chloro‐4‐phenyl) thiomethylene bisphosphonic acid (SR41319B) on the mononuclear cell factor mediated release of neural proteinases by articular chondrocytes and synovial cells. Biochemical Pharmacology 34:4043-4049.
Barbier A, Emonts‐Alt X, Breliere JC, Ethgen D (1990) In vitro and in vivo osseous pharmacological profile of tiludronate. Implications for osteoporosis treatment. Osteoporosis 1990 , Christiansen C, Overgaard K, Osteopress ApS, Copenhagen; 1127-1130.
Emonts‐Alt X, Barbier A, Breliere JC, Roncucci R (1985) Anti‐arthritic and anti‐osteoporotic activities of (chloro‐4‐phenyl)thiomethylene bisphosphonic acid (SR41319B). Pharmacological studies. Calcif Tissue Int 38:S34.
Charhon S, Meunier P, Ethgen D, Lacheretz F, Breliere JC, Roncucci R (1985) Histomorphometric analysis of bone biopsies of baboons treated with SR41319B, a new diphosphonate. Calcif Tissue Int 38:S33.
Geusens P, Nijs J, Van Der Perre G, Van Audekercke R, Lowet G, Govaerts S, Barbier A, Lacheretz F, Remandet B, Jiang Y, Dequeker J (1992) Longitudinal effects of tiludronate on bone mineral density, resonance frequency, and strength in monkeys. J Bone Miner. Res. 7:599-610.
Reginster JY, Jeugmans‐Huynen AM, Albert A, Denis D, Deroisy R, Lecart MP, Fontaine MA, Collette J, Franchimont P (1988) Biological and clinical assessment of a new bisphosphonate, (chloro‐4‐phenyl)thiomethylene bisphosphonate, in the treatment of Paget's disease of bone. Bone 9:349-354.
Audran M, Clochon P, Ethgen D, Renier JC (1989) Treatment of Paget's disease of bone with (4‐chloro‐phenyl)thiomethylene bisphosphonate. Clin Rheumatol 8:71-79.
Reginster JY, Colson F, Morlock G, Combes B, Ethgen D, Geusens P (1992) Evaluation of the efficacy and safety of oral tiludronate in Paget's disease of bone. A double blind, multiple dosage, placebo controlled study. Arthritis Rheum 35:967-974.
Reginster JYL (1992) Oral tiludronate: Pharmacological properties and potential usefulness in Paget's disease of bone and osteoporosis. Bone 13:351-354.
Nordin BEC (1978) Diagnostic procedures in disorders of calcium metabolism. Clin Endocrinol (Oxf) 8:55-67.
Huskisson EC (1974) Measurement of pain. Lancet 2:1127-1131.
Alexandre C, Chapuy MC, Bressot C, Vignon E, Arlot M, Mathieu L, Edouard C, Johnston CC, Meunier PJ (1980) Traitement de la maladie osseuse de Paget par l'éthane‐1 hydroxy‐1, 1 diphosphonate à faible posologie. Nouv Presse Med 9:3429-3433.
Khairi MRA, Altman RD, De Rosa GP, Zimmerman J, Schenk RK, Johnston CC (1977) Sodium etidronate in the treatment of Paget's disease of bone. Ann Intern Med 87:656-663.
Alexandre C, Meunier PJ, Edouard C, Khairi MRA, Johnston CC (1981) Effects of ethane‐1, hydroxy‐1, 1‐diphosphonate (5 mg/kg/day dose) on quantiative bone histology in Paget's disease of bone. Metab Bone Dis 4:309-316.
Reginster JY, Gritten C, Diverse P, Hauwaert C, Crielaard JM, Halleux R, Franchimont (1985) Traitement de la maladie osseuse de Paget par l'étidronate disodique (EHDP) à faible dose (5 mg/kg, par jour). Rev Rhum Mal Osteoartic 52:145-150.
Gibbs JC, Aron JE, Peacock M (1986) Osteomalacia in Paget's disease treated with short term, high dose sodium etidronate. BMJ 292:1227-1229.
de Deuxchaisnes, Rombouts‐Lindemans C, Huaux JP, Esselinckx W, Devogelaer JP, Malghen J, Maldague B (1982) Treatment of Paget's disease with the diphosphonate APD. A biological and radiological study. Diphosphonates and Bone , Donath A, Courvoisier B, Med. Hygiène, CEMO. Publ., Geneva; 303-327.
Mautalen CA, Gonzalez D, Ghirighelli G (1985) Efficacy of the bisphosphonate APD in the control of Paget's disease of bone. Bone 6:429-432.
Chapuy MC, Charhon S, Meunier PJ (1983) Sustained biochemical effects of short treatment of Paget's disease of bone with dichloromethylene disphosphonate. Metab Bone Dis 4:325-327.
Frazer TRC, Ibbertson HF, Holdaway IM, Rutland M, King A (1984) Effective oral treatment of severe Paget's disease of bone with APD (3‐amino‐1‐hydroxypropylidene‐1, 1‐bisphosphate): a comparison with combined calcitonin + EHDP. Australian and New Zealand Journal of Medicine 14:811-818.
Frijlink WB, Bijvoet OLM, Tevelde J, Heynen G (1979) Treatment of Paget's disease with (3‐amino‐1‐hydroxypropylidene)‐1, 1‐bisphosphonate (APD). Lancet 1:799-803.
Thiebault D, Jaeger P, Burckhardt P (1987) Paget's disease of bone treated in five days with AHPrBP (APD) per os. J Bone Miner Res 2:45-52.
Atkins RM, Yates AJT, Gray RES, Urwin GH, Hamdy NAT, Beneton MNC, Rosini S, Kanis JA (1987) Aminohexame diphosphonate in the treatment of Paget's disease of bone. J Bone Miner Res 2:273-279.
Harinck HIJ, Papapoulos SE, Blanksma HJ, Moolenaar AJ, Vermeij P, Bijvoet OLM (1987) Paget's disease of bone: early and late responses to three different modes of treatment with aminohydroxypropylidene bisphosphonate (APD). BMJ 295:1301-1305.
Lecart MP, Reginster JY, Deroisy R, Denis D, Franchimont P (1989) Cure brève (5 jours) de chloro 4 phenyl thiomethylène bisphosphonate à doses croissantes (600 mg/j, 800 mg/j, 1200 mg/j) dans la maladie osseuse de Paget. La Maladie Osseuse de Paget: Actualités , Simon L, Sebert JL, Herisson C, Masson, Paris; 241-245.
Reginster JY, Deroisy R, Denis D, Collette J, Lecart MP, Sarlet N, Ethgen D, Franchimont P (1989) Prevention of postmenopausal bone loss by tiludronate. Lancet 2:1469-1471.
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.