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Table 1: Diagnostics for Renal Osteodystrophy and Osteomalacia
High-turnover ROD Mixed-uraemic ROD Low-turnover ROD Osteomalacia
Bone formation Medium to high High Low Low
Mineralisation Normal Abnormal Normal Abnormal
Bone volume Low to high Low to normal Low to medium Low to medium
acid phosphatase (TRACP), telopeptides and pyridinolin crosslinks. seem to be associated with fewer systemic complications and might be
TRACP is produced by osteoclasts and a number of other organs. Its used alone or in combination with low-dose calcium-containing
sensitivity and specificity for high-turnover bone disease is 80 and 96%, phosphate binders. The activity of the parathyroid gland can also be
respectively, which is similar to that of other markers.
Telopeptides and reduced by increasing the sensitivity of the calcium-sensing receptor by
pyridinolin crosslinks are eliminated by the kidney and are therefore a calcimimetic. Because these drugs are very costly, they should be used
increased in renal failure.
Both molecules are collagen degradation only in therapy-resistant cases. Bisphosphonates inhibit osteoclast
products and are produced during osteoclastic bone resorption. The activity and reduce bone turnover and might therefore be the ideal
diagnostic value of telopeptides and pyridinolin crosslinks is unknown, treatment for high-turnover bone disease.
In addition, a reduction of
and these markers are used in the diagnosis and follow-up of vascular calcification during bisphophonate therapy has been reported.
osteoporosis rather than in renal bone diseases. In a small study, a significant increase of bone density was described
during the treatment with pamidronate in patients with clearly elevated
Treatment of Renal Osteodystrophy intact PTH serum levels (>500pg/ml).
The increase of intact PTH serum
In renal patients with decreased bone mineral density, diagnosis of the levels after bisphosphonate infusion could be disadvantageous and
underlying bone disease is a precondition for treatment. Measurement of might lead to therapy resistance. Additional and larger studies will
bone density alone will be insufficient, because all kinds of ROD are therefore be necessary in order to investigate the effect of
accompanied by a similar loss of bone density. A decreased bone mineral bisphosphonates on fractures or cardiovascular complications.
density, whether measured by dual-energy absorptiometry, quantitative Treatment options for low-turnover ROD are scarce. Currently, only the
computer tomography, sonography or magnetic resonance imaging, will reduction of parathyroid-gland-inhibiting medications (calcitriol and
therefore not discriminate between the different aetiologies. calcium) is recommended. Because the majority of patients with low-
turnover ROD have a relative or absolute deficiency of PTH, the
To reduce the high PTH level, patients should be treated with active administration of recombinant PTH, which is being used in osteoporosis,
vitamin (if the serum phosphate is <4.6mmol/l (eGFR between 15 and might be promising.
60ml/min) or <5.5mmol/l (haemodialysis)) and/or with different
Aluminium- and calcium-containing phosphate In a small and as yet unpublished pilot study with haemodialysis patients, a
binders have been increasingly abandoned – the former because of their positive influence of recombinant PTH on bone density was seen. BMP-7 has
influence on bone (low turnover) and the brain (dementia), and the been shown to be effective in rodents, but human studies are still lacking.
latter because of the increased frequency of vascular calcification. Bisphosphonates should be avoided because of their inhibition of bone
Newer phospshate binders such as sevelamer or lanthanum carbonate turnover and the risk of the worsening of adynamic bone disease. ■
1. Silver J, Kilav R, Naveh-Many P, Mechanisms of secondary 2002;62:1196–1207. bone remodeling in uremic patients, Kidney Int, 1999;55:
hyperparathyoidism, Am J Physiol Renal Physiol, 2002;283: 10. UreÒa P, Kubrusly M, Mannstadt M, et al., The renal 2141–56.
F367–76. PTH/PTHrP receptor is down-regulated in rats with chronic renal 20. Ureña P, Hruby M, Ferreira A, et al., Plasma total versus bone
2. Brown EM, Mechanisms underlying the regulation of failure, Kidney Int, 1994;45:605–11. alkaline phosphatase as markers of bone turnover in
parathyroid hormone secretion, Curr Opin Nephrol Hypertens, 11. National Kidney Foundation, K/DOQI Clinical Practice Guidelines hemodialysis patients, J Am Soc Nephrol, 1996;7:506–12.
1993;2:541–51. for Bone Metabolism and Disease in Chronic Kidney Disease, 21. Coen G, Bonucci E, Ballanti P, et al., PTH 1-84 and PTH
3. Almaden Y, Felsenfeld A, Rodriguez M, et al., Proliferation in Am J Kidney Dis, 2003;42:S1–S201. “7–84” in the noninvasive diagnosis of renal bone disease, Am
hyperplastic human and normal rat parathyroid glands: role of 12. Bushinsky DA, Wolbach W, Sessler NE, et al., Physicochemical J Kidney Dis, 2002;40:348–54.
phosphate, calcitriol and gender, Kidney Int, 2003;64:2311–17. effects of acidosis on bone calcium flux and surface ion 22. Coen G, Ballanti P, Balducci A, et al., Serum osteoprotegerin and
4. Almaden Y, Hernandez A, Torregrosa V, et al., High phosphate composition, J Bone Miner Res, 1993;8:93–102. renal osteodystrophy, Nephrol Dial Transplant, 2002;17:233–8.
level directly stimulates parathyroid hormone secretion and 13. Bichara M, Mercier O, Borensztein P, et al., Acute metabolic 23. Hannon RA, Clowes JA, Eagleton AC, et al., Clinical
synthesis by human parathyroid tissue in vitro, J Am Soc acidosis enhances circulating parathyroid hormone, which performance of immunoreactive tartrate-resistant acid
Nephrol, 1998;9:1845–52. contributes to the renal response against acidosis in the rat, phosphatase isoform 5b as a marker of bone resorption, Bone,
5. Mathew S, Davies M, Lund R, et al., Function and effect of J Clin Invest, 1990;86:430–43. 2004;34:187–94.
bone morphogenetic protein-7 in kidney bone and the bone- 14. Malluche H, Faugere MC, Renal bone disease 1990: an unmet 24. Mazzaferro S, Pasquali M, Ballanti P, et al., Diagnostic value of
vascular links in chronic kidney disease, Eur J Clin Invest, challenge for the nephrologist, Kidney Int, 1990;38:193–211. serum peptides of collagen synthesis and degradation in
2006;36:43–50. 15. Sherrard DJ, Hercz G, Pei Y, et al., The spectrum of bone dialysis renal osteodystrophy, Nephrol Dial Transplant,
6. Lund RJ, Davies MR, Brown AJ, et al., Successful treatment of disease in end-stage renal failure—an evolving disorder, Kidney 1995;10:52–8.
an adynamic bone disorder with bone morphogenetic protein-7 Int, 1993;43:436–42. 25. Martinez I, Saracho R, Montenegro J, et al., The importance of
in a renal ablation model, J Am Soc Neph, 2004;15:359–69. 16. Moe S, Drueke T, Cunningham J, et al., Definition, evaluation, dietary calcium and phosphorus in the secondary
7 Gonzalez EA, Lund RJ, Martin KJ, et al., Treatment of a murine and classification of renal osteodystrophy: a position statement hyperparathyroidism of patients with early renal failure, Am J
model of high-turnover renal osteodystrophy by exogenous from Kidney Disease: Improving Global Outcomes (KDIGO), Kidney Dis, 1997;29:496–502.
BMP-7, Kidney Int, 2002;61:1322–31. Kidney Int, 2006;69:1945–53. 26. Torregrosa JV, Moreno A, Mas M, et al., Usefulness of
8. Fukuda N, Tanaka H, Tominaga Y, et al., Decrease 1,25- 17. Malluche H, Monier-Faugere MC, The role of bone biopsy in the pamidronate in severe secondary hyperparathyroidism in
dihydroxyvitamin D3 receptor density is associated with a more management of patients with renal osteodystrophy, J Am Soc patients undergoing hemodialysis, Kidney Int Suppl,
severe form of parathyroid hyperplasia in chronic uremic Nephrol, 1994;4:1631–42. 2003;85:S88–90.
patients, J Clin Invest, 1993;92:1436–42. 18. Faugere MC, Malluche HH, Comparison of different bone-biopsy 27. Nitta K, Akiba T, Suzuki K, et al., Effects of cyclic intermittent
9. Tokumoto M, Tsuruya K, Fukuda K, et al., Reduced p21,p27 techniques for qualitative and quantitative diagnosis of metabolic etidronate therapy on coronary artery calcification in patients
and vitamin D receptor in the nodular hyperplasia in patients bone diseases, J Bone Joint Surg Am, 1983;65:1314–18. receiving long-term hemodialysis, Am J Kidney Dis,
with advanced secondary hyperparathyroidism, Kidney Int, 19. UreÒa P, De Vernejoul MC, Circulating biochemical markers of 2004;44:680–88.
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