Drug induced osteoporosis

Česká verzia

Authors: I. Žofková
Authors place of work: Endokrinologický ústav Praha, ředitelka doc. RNDr. Běla Bendlová, CSc.
Published in the journal: Vnitř Lék 2013; 59(1): 59-63
Category: Review

Summary

Loss of bone mass resulting from the treatment of chronic diseases is not unusual. However, osteoporosis in such patients is typically diagnosed too late, usually after a fracture appears. Particular attention should be given to glucocorticoids, which are commonly used in internal medicine. These hormones delay bone formation (via inhibition of osteoblast differentiation and osteoblast function) and activate bone resorption (through RANKL). Moreover, glucocorticoids inhibit calcium absorption from the intestines, which results in hypocalcemia. Following hyperparathyroidism further accelerates bone resorption. Severe damage to bone microstructure and its mechanical characteristics leads to atraumatic fractures. Bone loss sustained during glucocorticoid treatment occurs very early (3–5 % of bone mass in the first year and up to 1 % each year thereafter). Fortunately, most skeletal damage is reversible with early supplementation of vitamin D and calcium. Osteopenia (osteoporosis) complicates long-term treatment with supressive doses of thyroid hormone most often in females with hypoestrinism. L-thyroxine administered in doses > 0.093 mg/day leads to bone resorption, which is in part due to suppressed (low) levels of TSH. Medications which pose a high risk of fracture are those which induce hypoestrinism (aromatase inhibitors) and antiandrogens (GnRH agonists). Similarly, some oral antidiabetics (such as thiazolindiones) promote adipogenesis to the detriment of osteogenesis, which increases bone loss. Fractures are also frequently observed in patients treated with selective serotonin reuptake inhibitors, anti-epileptics, diuretics, anticoagulation drugs and proton pump inhibitors. This review discusses the mechanisms of bone damage induced by the above-mentioned pharmaceuticals.

Key words:
bone damage – glucocorticoids – thyroid hormone – aromatase inhibitors – GnRH agonists – thiazolidindiones – selective serotonin reuptake inhibitors – proton pump inhibitors

Zdroje

1. Migliaccio S, Brama M, Formari R et al. Glucocorticoid-induced osteoporosis: an osteoblastic disease. Aging Clin Exp Res 2007; 19: (3 Suppl.): 5–10.

2. Wasilewska A, Rybi-Szuminska A, Zoch-Zwierz W. Serum RANKL, osteoprotegerin (OPG), and RANKL/OPG ratio in nephrotic children. Pediatr Nephrol 2010; 25: 2067–2075.

3. McCarthy TL, Chang WZ, Liu Y et al. Runx2 integrates estrogen activity in osteoblasts. J Biol Chem 2003; 278: 43121–43129.

4. Rosen CJ, Bouxsein ML. Mechanisms of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol 2006; 2: 35–43.

5. Weinstein RS. Glucocorticoid-induced osteonecrosis. Endocrine 2012; 41: 183–190.

6. Kaneko K, Kawai S. Mechanisms and therapeutics of glucocorticoid-induced osteoporosis. Nihon Rinsho Meneki Gakkai Kaishi 2011; 34: 138–148.

7. Lau AN, Adachi JD. Role of teriparatide in treatment of glucocorticoid-induced osteoporosis. Ther Clin Risk Manag 2010; 6: 497–503.

8. Weinstein RS, Jilka RL, Almeina M et al. Intermitent parathyroid hormone administration counteracts the averse effects of glucocorticoids on osteoblast and osteocyte viability, bone formation, and strength in mice. Endocrinology 2010; 151: 2641–2649.

9. Štěpán J. Glukokortikoidy indukovaná osteoporóza. Vnitř Lék 2009; 55: 448–454.

10. Saito M, Marumo K, Ushiku C et al. Effects of alfacalcidol on mechanical properties and collagen cross-links of the femoral diaphysis in glucocorticoid-treated rats. Calcif Tissue Int 2011; 88: 314–324.

11. Ma Y, Nyman JS, Tao H et al. β2-adrenergic receptor signaling in osteoblasts contributes to the catabolic effect of glucocorticoids on bone. Endocrinology 2011; 152: 1412–1422.

12. Conradie MM, de Wet H, Kotze DD et al. Vynadate prevents glucocorticoid-induced apoptosis of osteoblasts in vitro and osteocytes in vivo. J Endocrinol 2007; 195: 229–240.

13. Jäger W, Xu H, Wlcek K et al. Gender- and dose-related effects of cyclosporin A on hepatic and bone metabolism. Bone 2012; 50: 140–148.

14. Mohammedi A, Omrani L, Omrani LR et al. Protective effect of folic acid on cyclosporine-induced bone loss in rats. Transpl Int 2012; 25: 127–133.

15. Pirro M, Manfredini MR, Scarponi AM et al. Association between thyroid hormone levels, the number of circulating osteoprogenitor cells, and bone mineral density in euthyroid postmenopausal women. Metabolism 2012; 61: 569–576.

16. Mysliwiec J, Adamczyk M, Nikolajuk A et al. Interleukin-6 and its considerable role in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in postmenopausal women. Endokrynol Pol 2011; 62: 299–302.

17. Gogakos AI, Duncan Bassett JH, Williams GR. Thyroid and bone. Arch Biochem Bipohys 2010; 503: 129–136.

18. Servitja S, Nogués X, Pietro-Alhambra D et al. Bone health in a prospective cohort of postmenopausal women receiving aromatase inhibitors for early breast cancer. Breast 2012; 21: 95–101.

19. Ahlborg HG, Nguen ND, Center JR et al. Incidence and risk factors for low trauma fractures in men with prostate cancer. Bone 2008; 43: 856–860.

20. Montagnani A, Gonnelli S, Alessandri M et al. Osteoporosis and risk of fracture in patients with diabetes: an update. Aging Clin Exp Res 2011; 23: 84–90.

21. Sardone LD, Renlund R, Willett TL et al. Effect of rosiglitazone on bone quality in a rat model of insulin resistence and osteoporosis. Diabetes 2011; 60: 3271–3278.

22. Yadav VK, Ducy P. Lrp5 and bone formation: A serotonin-dependent pathway. Ann NY Acad Sci 2010; 1192: 103–109.

23. Westbroek I, van der Plas A, de Rooij KE et al. Expression of serotonin receptors in bone. J Biol Chem 2001; 276: 28961–28968.

24. Diem SJ, Bieckwell TL, Stone KL et al. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med 2007; 167: 1240–1245.

25. Richards JB, Papaioannou A, Adachi JD et al. Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med 2007; 167: 188–194.

26. Ensrud KE, Walczak TS, Blackwell T et al. Antiepileptic drug use increases rates of bone loss in older women: a prospective study. Neurology 2004; 62: 2051–2057.

27. Andress DL, Ozuna J, Tirchwell D et al. Anti-epileptic drug-induced bone loss in young male patiens who have seizures. Arch Neurol 2002; 59: 781–786.

28. Kondo A, Togari A. In vivo stimulation of sympathetic nervous system modulates osteoblastic activity in mouse calvaria. Am J Physiol Endocrinol Metab 2003; 285: E661–667.

29. Pytlik M, Cegieta U, Norwińska B et al. Bone remodeling after administration of proton pump (H+/K+-ATPase) inhibitors and alendronate in ovariectomized rats. Acta Pol Pharm 2012; 69: 113–120.

30. Lau YT, Ahmed NN. Fracture risk and bone mineral density reduction associated with proton pump inhibitors. Pharmacotherapy 2012; 32: 67–79.