The bisphosphonates are used widely in osteoporosis. In patients with stage 4 CKD, one small study found a modest increase in the bone density of the spine after 18 months, but no change in the hip.7 This is different from the changes reported in many studies of postmenopausal osteoporosis showing increases in both hip and spine. Furthermore, in CKD patients, bone loss typically is in the cortical bone, and bone density in the spine is normal but the radius and hip are low. There is no evidence of a beneficial effect of bisphosphonate in these patients, but sometimes there is a physiologic rationale for using them. Bisphosphonates are a reasonable choice for patients who have fractures, bone loss, and high bone turnover despite good control of PTH, calcium, and phosphate. A bone biopsy would reassure the clinician that bone turnover was high. The biochemical markers of bone (e.g., bone specific alkaline phosphatase and C-telopeptide) have modest predictive values in patients with CKD-MBD.

Gonadal hormones and analogs probably help bone—even in the presence of renal failure—but evidence in patients remains limited. Raloxifene has the potential to improve spinal bone density in dialysis patients.6 This medication works through the estrogen receptors and theoretically should benefit women regardless of renal function. This is a rational choice for patients without an elevated risk of clotting. In premenopausal or perimenopausal women, estrogen probably will help bone. The dose should be half that used for normal women.9 In hypogonadal men, testosterone could be considered.


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In conclusion

Before the debut of penicillin, clinicians treated syphilis with a variety of medicines that are no longer used today. In the future, drugs must be found that can treat the basic causes of the bone disease in patients with CKD-MBD. Antibodies to sclerostin hold promise as anabolic agents to strengthen the bone.10 Additional research should be performed on such bone-growth factors as bone morpho­genetic protein 7.11 We know that there are striking abnormalities in levels of fibroblast growth factor 23 and klotho, but the effects of these newly defined hormones remain unknown.12 Our hope is that the next generation of clinicians will have better medications to use for their patients with poor bone strength.

Dr. Ott is professor of medicine at the University of Washington in Seattle.

References

1. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009;113:S1-130.

2. Ott SM. Bone histomorphometry in renal osteodystrophy. Semin Nephrol. 2009;29:122-32.

3. Jamal SA, Bauer DC, Ensrud KE, et al. Alendronate treatment in women with normal to severely impaired renal function: an analysis of the fracture intervention trial. J Bone Miner Res. 2007;22:503-508.

4. Miller PD, Roux C, Boonen S, et al. Safety and efficacy of risedronate in patients with age-related reduced renal function as estimated by the Cockcroft and Gault method: a pooled analysis of nine clinical trials. J Bone Miner Res. 2005;20:2105-2115.

5. Miller PD, Schwartz EN, Chen P, et al. Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment. Osteoporos Int. 2007;18:59-68.

6. Hernández E, Valera R, Alonzo E, et al. Effects of raloxifene on bone metabolism and serum lipids in postmenopausal women on chronic hemodialysis. Kidney Int. 2003;63:2269-2274. Available at www.nature.com/ki/journal/v63/n6/full/4493700a.html.

7. Toussaint ND, Lau KK, Strauss BJ, et al. Effect of alendronate on vascular calcification in CKD stages 3 and 4: a pilot randomized controlled trial. Am J Kidney Dis. 2010;56:57-68.

8. Ott SM. Review article: Bone density in patients with chronic kidney disease stages 4-5. Nephrology (Carlton). 2009;14:395-403.

9. Stehman-Breen C, Anderson G, Gibson D, et al. Pharmacokinetics of oral micronized beta-estradiol in postmenopausal women receiving maintenance hemodialysis. Kidney Int. 2003;64:290-294. Avialable at www.nature.com/ki/journal/v64/n1/full/4493871a.html.

10. Padhi D, Jang G, Stouch B, et al. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2010 (published online ahead of print).

11. Davies MR, Lund RJ, Mathew S, Hruska KA. Low turnover osteodystrophy and vascular calcification are amenable to skeletal anabolism in an animal model of chronic kidney disease and the metabolic syndrome. J Am Soc Nephrol. 2005;16:917-928. Available at jasn.asnjournals.org/content/16/4/917.long.

12. van Husen M, Fischer AK, Lehnhardt A, et al. Fibroblast growth factor 23 and bone metabolism in children with chronic kidney disease. Kidney Int. 2010;78:200-206.

All electronic documents accessed November 15, 2010.