Osteoporosis is a skeletal disorder predominantly affecting postmenopausal women. Combination therapy of Carbocalcitonin (Elcatonin) and oral conjugated oestrogens (Premarin) not only prevents postmenopausal bone loss but leads to an increase in bone mass in normal early postmenopausal women. The aims of the study was to investigate the effect of combination therapy. A combination of Elcatonin (Carbo calcitonin) and Premarin was compared to Premarin alone, and to Elcatonin (Carbocalcitonin) alone and all groups were then compared to a control group.peer-reviewe

Albisetti, Walter

Barbacini, E.

Brincat, Mark P.

Crosignani, P.G.

Meschia, M.

Pietrogrande, V.

English

OAR@UM

Maltese Medical Journal 2l Volume n Issue I 1990 Postmenopausal Bone loss: Prevention and Replacement. M. Brincat *, M. Meschia**, E. Barbacini**, P.G. Crosignani**, W. Albisetti ***, Clinical trial on efficacy of a combination of elcatonin (carbocalcitonin) and conjugated oestrogens in postmenopausal normal early woman. Summary Combination therapy of Carbocalcitonin (Elcatonin) and oral conjugated oestrogens (Premarin) not only prevents postmenopausal bone loss but leads to an increase in bone mass in normal early postmenopausal women. Introduction Osteoporosis is a skeletal disorder predominantly affecting postmenopausal women. The physiologically balanced coupling mechanism of bone formation and bone resorption ensures the skeleton's integrity and renewal. Peak bone mass is reached in the fourth decade of life. In the early postmenopausal years there is an accelerated bone loss. By the age of 79 years a woman loses 50% of her bone mass while a man loses only 25% by the age of 90 (1). It is estimated that by the age of 65 some 40% of women would have experienced at least one osteoporotic fracture (2). This is due to a decline in bone organic matrix, the primary pathological event leading to osteoporosis (3). Oral oestrogen administration has been shown to arrest postmenopausal bone loss (4,5). However, it has been suggested that oestrogen treatment on its own win only reduce the risk of osteoporotic fractures by 50% (6). This is probably because therapy is started too late or bone mass at the start of the menopause in certain individuals lies within the low normal range. Calcitonin, like oestrogen, when used alone has also been shown to V. Pietrogrande*** CHANGES IN VERTEBRAL BONE MASS AFTER ONE YEARS TREATMENT (Dual Photon) (m,±,S.E.) 1.1 ** p<O.Ol* p<O.05 , 0 ** **I! ~ gm/cm 2 09 ~-r----l 08 07" r'------,-------~-----,------~ o 6 12 ~-B. Premalln+Caicllonln group (n;12) A, Calcnon,n group (n= lJ) Fig. 1. Changes in vertebral bane mass during one year's treatment with Premarin and Cakitonin compared to changes r.dth Cakitonin only. The significance levels shown indicate comparillon. with base line levels. prevent postmenopausal bone loss (7,8). Many treatment strategies have been developed in the management of postmenopausal bone loss aimed at maintaining bone mass. To date only limited work has been aimed at increasing bone mass. Aims The aims of the study was to investigate the effect of combination therapy on early postmenopausal bone loss. A combination of Elcatonin (Carbo calcitonin) and Premarin was compared to Premarin alone, and to Elcatonin (Carbocalcitonin) alone and all groups were then compared to a control group. RATIONALE OF TREATMENT Pa!itive Bone Former Osteoblastic (oestrogens) Activity" Increaae in Bone Mass An ti-Resorber Osteoblastic/ (Calcitonin) Activity Elcatonin Calcitonin is an endogenous 32 ­amino acid polypeptide hormone which binds to specific receptors on osteoclasts inhibiting bone resorption. Elcatonin (ISF) is a recently developed synthetic analogue of eel calcitonin with a greater stability to pH and temperature than other Calcitonins. Weight for weight Elcatonin is more biologically active than other calcitonins. Weight for weight Elcatonin is as biologically active as salmon and natural eel calcitonin. Patients and Methods *Department of Obstetrics and Gynaecology St. George's Hospital, London (currently Consultant at St. Luke's Hospital) ** III Department of Obstetrics and Gynaecology, University of Milan, ***Department of, Orthopaedics, University of Milan -Maltese Medical Journal 21 Volume IT Issue I 1990 CHANGES IN VERTEBRAL BONE. MASS AFTER ONE YEARS TREATMENT (Dual Photon) (m±S.E.) 12 ** p<O_O l * p<O ,Q5 10 1 i ~' gm/cm ' 0.9 1 ~ a. ~ 07 06 12 Months B,' Prema"n+Calc~onln g'oup In- ' 21 C, Premanll groop (n.9) Fig. H. Changes in verlebral bone maBB during one year. treatment with Premarin and Calcitonin compared 10 changes with Premarin only. The Bignificwwe /eve,. shown indicaIe compariIIonB with baBe line /evel& The patients were randomly assigned to one of the following treatment groups: Group A 40 MRCU of Elcatonin (1 ampoule) i.m. twice a week Group B 40 MRCU of Elcatonin (1 ampoule) im. twice a week associated with conjugated oestrogens l.25mg dailyo:ally, plus medroxyprogesterone acetate lOmg daily orally for 10 days monthly. Group C Conjugated oestrogens l.25mg daily orally plus medroxyprogesterone acetate lOmg daily orally for 10 days monthly. Group D no. treatment All the patients were normal women who were at least 6 months and not more than 10 years postmenopausal. Table 1 gives the patient data. Patients were recruited if they had clinical evidence of the menopause supported by a high plasma level of Follicle- stimulating Hormone (FSH value > 40 lUll). Patients were excluded from entering the study if they had any of the following: - Therapy . with sex steroids during the year preceding the admission to the study severe hepatic, renal, cardiac or gastroenterologic disease inflammatory or degenerative osteomuscular diseases (Paget's disease, osteomalacia, rheumatoid arthritis) alcoholism metabolic disorders (e.g. diabetes mellitus) unless under stable medical control (none in fact were involved) neoplastic disease treatment with drugs affecting bone metabolism in the 4 weeks preceding the inclusion in the study Patients were assessed at baseline and after 3, 6 and 12 months on the study. The following information was obtained before randomisation to treatment: - Age - Years since the onset menopause - Follicle - stimulating hormone (FSH) serum levels - Bone density of lumbar spine (L2 - IA) by Dual Beam Photon Absorptiometry CNorland) - Clinical ex&mination On the 3rd, 6h, and 12th month, a repeat assessment of the l'.ID1bar spine was carr.ed 01.>.1; using Dual Beam Phot.on Absorptiometry (Norland). This method was used to assess the bone density of L2 to IA. AlI'cases were assessed in a blind fashion by one of us (WN. The error in the method at the lumbar spine was calculated as being 1.5%. In this report we present the results of 44 patients who completed 1 year of follow up. (75 were originally admitted to the study and randomised to one of the treatment groups). The high rate of drop-outs (30%) is due to the long treatment duration and to the difficulties in getting full compliance from patients, especially since this involved a considerable amount of travelling. To our knowledge no patients have dropped out because of side effects, although some women on Calcitonin alone complained of flushes in the initial months of the study. Statistical Methods After testing for normality, statistical analysis was carried out using a paired Student's t-test. Across group comparisons at 0, 3, 6 and 12 months were carried out using a one-way analysis of variance. Results The results of the study are shown in Figures 1, 2 and 3. The Premarin and Elcatonin group showed a significant mean increase in vertebral bone mass of 11.24% at the end of one year's therapy. The Premarin only group showed a non-significant mean increase of 3.9% as did the Elcatonin only group(2.3%) at the end of one year s therapy. The control group showed a significant mean bone loss of 4.8% after being followed up for one year. There was no statistical significance in bone mass between the groups at the start of the study. Table (2) gives a comparison of the results on the different regimens at the end of one year's therapy. Conclusion and Discussion The data for the patients who completed 12 months of treatment, CA) Confirms that vertebral bont': mass is lost rapidly in the initial postmenopausal years (1). CB) Confirms that this loss can be prevented by either Oestrogens alone C4,5) or Calcitonin alone (7,8). CC) Indicates that Oestrogens CPremarin) and Carbocalcitonin CElcatonin) combined in adequate doses, not only prevents early postmenopausal bone loss but results in a significant gain. In our study the mean gain was of 11.2% after Maltese Medical Journal 21& Volume n Issue I 1990 one year. The indications are that most of this gain occurs in the first 6 months of therapy with levelling off then occurring. Although the clinical significance of such a gain in bone mass in the combined group in ear~ postmenopausal women stiIl needs to be assessed it would be logical to suggest the following !~men for women who are at a high risk of developing postmenopausal osteoporotic fractures:­(A) Combined therapy of Premarinl Gestogens + Elcatonin for the first year of treatment. (B) Maintenance of the bone mass after that with eight Premarinl Gestogen combinations alone or Elcatonin alone, depending on the overall clinical picture of the woman concerned. This therapeutic regimen is currently being analysed in a separate study. References 1. GORDAN G s. PREVEl'n'lON OF BONE WSS AND FRACTURES IN WOMEN. MATUJUTAS 1984 ; 6: 225-242. 2. CRlILY R.G., HORSMAN A, MARSHAIL DR. AND NORDIN BEC. BONE MASS IN POSTMENOPAUSAL WOMEN AFTER WITHDRAWAL OF OESTROGEN/GESTOGEN REPLACEMENT THERAPY. LANCET I: 1978; 459461. 3. BRINCAT M, MONIZ C. J., KABALAN S. ET AL . DECliNE IN SKIN COlLAGEN CONl'ENT AND METACARPAL INDEX AFTER THE MENOPAUSE AND ITS PREVENI'ION WITH SEX HORMONE REPLACEMENT. BRITISH JOURNAL OF OBSTETRICS AND GYNAECOWGY 1978; 94: 126·129. 4. LINDSAY R.. HART D.M., PURDEE D., FERGUSON M., CLARK AB. COMPARATIVE EFFECTS OF OESTROGEN AND PROGESTAGEN ON BONE LOSS IN POSTMENOPAUSAL WOMEN. CUNICAL SCIENCE AND MOLECULAR MEDICINE 1978; 54: 193-198. 5. NATCHIGALL 1..E., NATCHIGALL KH., NATCHlGALL RD., BECHMAN E. ESTROGEN REPLACEMENT THERAPY: A 10 YEAR PROSPEC71VE STUDY IN THE RESPONSE TO OSTEOPOROSIS. OBSTETRICS AND GYNAECOWGY 1980; 53: 277·281. 6. ROSS R.K, PAGANINI·HILL A. MACH J.M. . REDUCTION IN FRACTURES AND OTHER EFFECTS OF ESTROGEN REPLACEMENT THERAPY IN HUMAN POPULATION. OSTEOPOROSIS. PROCEEDINGS OF THE COPENHAGEN INrERNATlONAL SYMPOSIUM ON OSTEOPOROSIS 1984 ; 1: 289-297. 7. REGlN6vl'ER J.T, DENIS D., ALBERT R. ET AL INrRANASAL CALCITONIN: A NEW HORIZON IN PREVENTION IN GYNAECOLOGICAL ENDOCRINOLOGY EDS GENNAZANI AR., PETRAGUA F., VOLPE A, FACCJIlNE1'1'I F. rrHE PARTHENON PUnUSHlNG GROUP). 1988; ~ 593-601. 8. MACINTYRE I., STEVENSON J.C., WJIlTEHEAD M.l. ET AL CALCITONIN FOR PREVENTION OF POSTMENOPAUSAL BONE WSS. LANCET 1988; 1: 90().902. Fig. m. Clwngell in vertebral bone maBIl afkr one year in a group of postmenopausal uoman who were on no treatment. The copyright of this article belongs to the Editorial Board of the Malta Medical Journal. The Malta Medical Journal’s rights in respect of this work are as defined by the Copyright Act (Chapter 415) of the Laws of Malta or as modified by any successive legislation. Users may access this full-text article and can make use of the information contained in accordance with the Copyright Act provided that the author must be properly acknowledged.  Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder. This article has been reproduced with the authorization of the editor of the Malta Medical Journal (Ref. No 000001)  

Postmenopausal bone loss : prevention and replacement

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Postmenopausal bone loss : prevention and replacement

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