Abstract
A 2-year non-randomized prospective study was carried out in a teaching hospital menopause clinic to assess the effect on the skeleton of tibolone (Livial, Organon) 2.5 mg daily in recently postmenopausal women. One hundred women who were between 6 and 36 months since their last menstrual period and had raised gonadotrophin levels consistent with the menopause were allocated into two groups. One group received 2.5 mg tibolone daily and the other group no medication. Bone densitometry of the spine and femur was performed at 0, 6, 12 and 24 months and biochemical markers of bone metabolism were assessed at these points. Severity of hypo-oestrogenic symptoms was assessed at baseline and at 1 and 2 years. After 2 years there was a significant increase in bone mass as measured by dual energy X-ray absorptiometry (DXA) of 2.5% in the spine, and 3.5% in the neck of femur in the women who took tibolone (n=46), whereas in the control group (n=45) bone loss occurred (spine, 2.9%; femur, 3.7%). When these changes were compared they were significantly different for both sites (p<0.001). In the treatment group the urinary hydroxyproline/creatinine and calcium/creatinine ratios fell from 0.014 (0.002–0.027) to 0.010 (0.000–0.111) (mol/l) (mmol/l) (p<0.01) and 0.47 (0.08–0.96) to 0.33 (0.09–1.20) (mmol/l) (mmol/l) (p<0.001) respectively, while the serum osteocalcin and alkaline phosphatase decreased from 1.90 (0.20–4.70) to 1.00 (0.00–3.00) mmol/l (p<0.01) and 190 (92–301) to 138 (91–283) mmol/l (p<0.001) respectively. In conclusion we have found that tibolone given in the early postmenopausal years suppresses skeletal metabolism and prevents bone loss in both spine and femur. Tibolone therefore has a potentially important long-term role in the reduction of the incidence of osteoporotic fractures, particularly in view of the compliance that ‘bleed-free’ therapy will encourage.
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Fogelman I, Poser JW, Smith ML, et al. Alterations in skeletal metabolism following oophorectomy. In: Christiansen C et al., editors. Osteoporosis Glostrup, Denmark: Aalborg Stifstbog-trykkeri, 1984:519–22.
Heaney RP, Recker RR, Saville PD. Menopausal changes in bone remodelling. J Lab Clin Med 1978;92:964–70.
Lindsay R, Hart DM, Aitken JM, et al. Long-term prevention of postmenopausal osteoporosis by oestrogen: evidence for an increased bone mass after delayed onset of oestrogen treatment. Lancet 1976;1:1038–41.
Horsman A, Gallagher JC, Simpson M, Nordin BEC. Prospective trial of oestrogen and calcium in postmenopausal women. BMJ 1977;2:789–92.
Recker RR, Saville PD, Heaney RP. Effect of oestrogen and calcium carbonate on bone loss in postmenopausal women. Ann Intern Med 1977;87:649–55.
Christiansen C, Christiansen MS, McNair P, et al. Prevention of early postmenopausal bone loss: controlled 2-year study in 315 normal females. Eur J Clin Invest 1980;10:273–9.
Genant HK, Cann CE, Ettinger B, Gordan GS. Quantitative computed tomography of vertebral spongiosa: a sensitive method for detecting early bone loss after oophorectomy. Ann Intern Med 1982;97:699–705.
Nachtigall LE, Nachtigall RH, Nachtigall RD, Beckman EM. Oestrogen replacement therapy: a 10 year prospective study in the relationship to osteoporosis. Obstet Gynecol 1979;53:277–81.
Stevenson JC, Cust MP, Gangar KF, et al. Effects of transdermal versus oral hormone replacement therapy on bone density in spine and proximal femur in postmenopausal women. Lancet 1990;336:265–9.
Spector TD. Use of oestrogen replacement therapy in high risk groups in the United Kingdom. BMJ 1989;299:1434–5.
Wren BG, Brown L. Compliance with hormone replacement therapy. Maturitas 1990;13:17–21.
Vies van der J. Pharmacological studies with OD 14. Maturitas (Suppl) 1987;1:15–24.
Visser J de, Coert A, Feenstra H, Vies J van der. Endocrinological studies with Org OD 14. Arzneimittelforsch/Drug Res 1984;34:1010–7.
Genazzani AR, Benedek-Jaszman LJ, Hart DM, et al. Org OD 14 and the endometrium. Maturitas 1991;13:243–51.
Trevoux R, Dieulangard P, Blum A. Efficacy and safety of ORG OD 14 in the treatment of climacteric complaints. Maturitas 1983;5:89–96.
Linday R, Hart DM, Kraszewski A. Prospective double-blind trial of synthetic steroid (ORG OD 14) for preventing postmenopausal osteoporosis. BMJ 1980;1:1207–9.
Bergman I, Loxley R. The determination of hydroxyproline in urine hydroxylates. Clin Chim Acta 1970;27:347–9.
NIPO Survey. Menopause. Nourypharma Nederland BV 1990; R-808. NIPO.
Rymer J, Chapman MG, Fogelman I. The incidence of vaginal bleeding with tibolone treatment. Br J Obstet Gynaecol 1994;101:53–56.
Geusens P, Dequeker J, Gielen J, Schot LPC. Non-linear increase in vertebral density induced by a synthetic steroid (ORG OD 14) in women with established osteoporosis. Maturitas 1991;13:155–62.
Watts NB, Harris ST, Genant HK, et al. Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. N Engl J Med 1990;323:73–9.
Riggs BL, Seeman E, Hodgson SF, et al. Effect of the fluoride/ calcium regime on vertebral fracture occurrence in postmenopausal osteoporosis. N Engl J Med 1982;306:446–50.
Storm T, Thamsborg G, Steiniche T, et al. Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med 1990;322:1265–71.
Naessen T, Persson I, Ljunghall S, Bergstrom R. Women with climacteric symptoms: a target group for prevention of rapid bone loss and osteoporosis. Osteoporosis Int 1992;2:225–31.
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Rymer, J., Chapman, M.G. & Fogelman, I. Effect of tibolone on postmenopausal bone loss. Osteoporosis Int 4, 314–319 (1994). https://doi.org/10.1007/BF01622189
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DOI: https://doi.org/10.1007/BF01622189