Skip to main content

Advertisement

Log in

Bone loss after liver transplantation is not prevented by cyclical etidronate, calcium and alphacalcidol

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

After orthotopic liver transplantation (OLT) bone mass rapidly declines and vertebral fracture rate increases. We studied bone loss and parameters of bone turnover in 53 consecutive patients. In an attempt to reduce bone loss the patients were prophylactically treated with cyclical etidronate in addition to daily 1α-hydroxyvitamin D3 and calcium. During the first 3 months after transplantation median lumbar spinal bone mineral density (BMD) decreased 4.5%; subsequently no significant changes occurred. Median hip BMD continued to fall during the first post-transplantation year and deteriorated 7% over the whole study period. New vertebral fractures were seen in 25% of the patients, which is not lower than previously reported rates in patients not receiving cyclical etidronate. Parathyroid hormone levels increased after OLT (p=0.01), but remained within normal ranges. Urinary hydroxyproline levels were increased and normalized in the second half-year after OLT. Elevated fasting calciuria increased further after OLT. 1,25-Dihydroxy-vitamin D3 levels were lowered pre-OLT (25 vs 66 pmol/1,p<0.001) and normalized at 3 months after OLT. Serum osteocalcin concentrations remained unchanged and were reduced compared with levels in healthy controls. In summary, increased bone resorption occurs after OLT with persistent decreased bone formation, leading to vertebral fracture in 25% of patients. Etidronate, 1α-calcidol and calcium treatment did not prevent bone loss.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hodgson SF, Dickson ER, Wahner HW, Johnson KA, Mann KG, Riggs BL. Bone loss and reduced osteoblast function in primary biliary cirrhosis. Ann Intern Med 1985;103:855–61.

    Google Scholar 

  2. Bikle DD, Genant HK, Cann C, Recker RR, Halloran BP, Strewler GJ. Bone disease in alcohol abuse. Ann Intern Med 1985;103:42–8.

    Google Scholar 

  3. Stellon AJ, Webb A, Compston J, Williams R. Low bone turnover state in primary biliary cirrhosis. Hepatology 1987;7:137–42.

    Google Scholar 

  4. Stellon AJ, Webb A, Compston JE. Bone histomorphometry and structure in corticosteroid treated chronic active hepatitis. Gut 1988;29:378–84.

    Google Scholar 

  5. Diamond TH, Stiel D, Lunzer M, McDowall D, Eckstein RP, Posen S. Hepatic osteodystrophy: static and dynamic bone histomorphometry and serum bone Gla-protein in 80 patients with chronic liver diseases. Gastroenterology 1989;96:213–21.

    Google Scholar 

  6. Diamond T, Stiel D, Lunzer M, Wilkinson M, Roche J, Posen S. Osteoporosis and skeletal fractures in chronic liver disease. Gut 1990;31:82–7.

    Google Scholar 

  7. Hodgson SF, Dickson ER, Eastell R, Eriksen EF, Bryant SC, Riggs BL. Rate of cancellous bone remodelling and turnover in osteopenia associated with primary biliary cirrhosis. Bone 1993;14:819–27.

    Google Scholar 

  8. Haagsma EB, Thijn CJP, Post JG, Slooff MJH, Gips CH. Bone disease after orthotopic liver transplantation. J Hepatol 1988;6:94–100.

    Google Scholar 

  9. Porayko MK, Wiesner RH, Hay JE, Krom RAF, Beaver S, Schwerman L. Bone disease in liver transplant recipients: incidence, timing, and risk factors. Transplant Proc 1991;23:1462–5.

    Google Scholar 

  10. Arnold JC, Hauser D, Ziegler R, et al. Bone disease after liver transplantation. Transplant Proc 1992;24:2709–10.

    Google Scholar 

  11. Eastell R, Rolland Dickson E, Hodgson SF, et al. Rates of vertebral bone loss before and after liver transplantation in women with primary biliary cirrhosis. Hepatology 1991;14:296–300.

    Google Scholar 

  12. Hughes H, Hagen L, Sutton RAL. Liquid-chromatographic determination of 4-hydroxyproline in urine. Clin Chem 1986;32:1002–4.

    Google Scholar 

  13. Pak CYC, Kaplan R, Bone H, Townsend J, Waters O. A simple test for the diagnosis of absorptive, resorptive and renal hypercalciurias. N Engl J Med 1975;292:497–500.

    Google Scholar 

  14. Riggs BL, Wahner HW, Dunn WL, Mazess RB, Offord KP, Melton LJ. Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis. J Clin Invest 1981;67:328–35.

    Google Scholar 

  15. McDonald JA, Dunstan CR, Dilworth P, et al. Bone loss after liver transplantation. Hepatology 1991;14:613–9.

    Google Scholar 

  16. Storm T, Thamsborg G, Steiniche T, Genant HK, Sorensen OH. 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.

    Google Scholar 

  17. Watts NB, Harris ST, Genant HK, et al. Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. N Engl J Med 1990;323:73–9.

    Google Scholar 

  18. Suzuki Y, Ichikawa Y, Saito E, Homma M. Importance of increased urinary calcium excretion in the development of secondary hyperparathyroidism of patients under glucocorticoid therapy. Metabolism 1983;32:151–6.

    Google Scholar 

  19. Reid IR, Ibbertson HK. Evidence of decreased tubular reabsorption of calcium in glucocorticoid-treated asthmatics. Horm Res 1987;27:200–4.

    Google Scholar 

  20. Bikle DD, Gee E, Halloran BP, Ryzen E, Haddad JH. Free 1,25-dihydroxyvitamin D levels in serum from normal subjects, pregnant subjects, and subjects with liver disease. J Clin Invest 1984;74:1966–71.

    Google Scholar 

  21. Diamond T, Stiel D, Mason R, et al. Serum vitamin D metabolites are not responsible for low turnover osteoporosis in chronic liver disease. J Clin Endocrinol Metab 1989;69:1234–9.

    Google Scholar 

  22. Rabinovitz M, Shapiro J, Lian J, Block GD, Merkel IS, Van Thiel DH. Vitamin D and osteocalcin levels in liver transplant recipients. Is osteocalcin a reliable marker of bone turnover in such cases? J Hepatol 1992;16:50–5.

    Google Scholar 

  23. Brown JP, Delmas PD, Malaval L, Edouard C. Chapuy MC, Meunier PJ. Serum bone Gla-protein: a specific marker of bone formation in postmenopausal osteoporosis. Lancet 1984;1:1091–3.

    Google Scholar 

  24. Watson RGP, Coulton L, Kanis JA, et al. Circulating osteocalcin in primary biliary cirrhosis following liver transplantation and during treatment with cyclosporin. J Hepatol 1990;11:354–8.

    Google Scholar 

  25. Kelly PJ, Sambrook PN, Eisman JA. Potential protection by cyclosporin against glucocorticoid effects on bone. Lancet 1989;2:1388.

    Google Scholar 

  26. Morrison NA, Shine J, Fragonas JC, Verkest V, McMenemy ML, Eisman JA. 1,25-Dihydroxyvitamin D-responsive element and glucocorticoid repression in the osteocalcin gene. Science 1989;246:1158–61

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Riemens, S.C., Oostdijk, A., van Doormaal, J.J. et al. Bone loss after liver transplantation is not prevented by cyclical etidronate, calcium and alphacalcidol. Osteoporosis Int 6, 213–218 (1996). https://doi.org/10.1007/BF01622737

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01622737

Keywords

Navigation