Pathogenesis and prevention of bone loss in patients who have kidney disease and receive long-term immunosuppression.
The coexistence of kidney disease with a need for immunosuppressive therapy leads to the convergence of several threats to bone. These comprise general effects of the primary disease, e.g., inflammatory state, more specific effects of acute renal failure or chronic kidney disease, and effects of therapies. Multisystem inflammatory disease that requires immunosuppression is associated frequently with kidney damage, and any reduction of kidney function that takes the patient into or beyond chronic kidney disease stage 2 for more than a short time is likely to have a negative impact on bone health. Bone mineral density frequently is low and fracture rates are high, although correlations often are poor. Chronic inflammation leads to local and systemic imbalance between bone formation and resorption. Upregulation of NF-kappabeta ligand (RANKL) and variable downregulation of osteoprotegerin are implicated, and bone health may improve in response to treatment of the inflammatory state. Certain immunosuppressive agents, especially glucocorticoids and calcineurin inhibitors, contribute further to bone loss. Antiresorptive agents such as bisphosphonates are used widely and, although able to prevent loss of bone mineral density, have uncertain effects on fracture rates. Augmentation of anabolic activity is desirable but elusive. Synthetic parathyroid hormone is untested but has potential. Manipulation of the RANKL/osteoprotegerin system now is feasible using antibodies to RANKL or synthetic osteoprotegerin. In the future, manipulation of the calcium-sensing receptor using calcimimetic or calcilytic agents may allow the anabolic effects of parathyroid hormone to be harnessed to good effect. With all of these therapies, it will be important to assess response in relation to important clinical end points such as fracture.
Cunningham
John
J
The Centre for Nephrology, The Royal Free Hospital, Pond Street, London NW3 2PF, UK. drjohncunningham@aol.com
D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy; D001851:Bone Diseases, Metabolic / Q000209:etiology* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007674:Kidney Diseases / Q000150:complications* / Q000188:drug therapy*; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy; D008297:Male; D014657:Vasculitis / Q000150:complications / Q000188:drug therapy
D007166:Immunosuppressive Agents