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Circulating Levels of Interleukin-6 Soluble Receptor Predict Rates of Bone Loss in Patients with Primary Hyperparathyroidism

Department of Medicine (I.A.N., M.A.M., K.I.), Section of Endocrinology, and Departments of Orthopedic Surgery (C.G.) and Surgery (B.K.), Yale University School of Medicine, New Haven, Connecticut 06520-8020; and Osteoporosis Center (R.L.), Hamden, Connecticut 06517

Address all correspondence and requests for reprints to: Karl Insogna, M.D., Yale School of Medicine, 333 Cedar Street, FMP 106, P.O. Box 208020, New Haven, Connecticut 06520-8020. E-mail: karl.insogna{at}yale.edu.

Abstract

It remains unclear whether mild primary hyperparathyroidism results in accelerated bone loss, with recent studies reaching different conclusions. This could be due to intrinsic differences in disease activity not captured by the classical biochemical markers of the disease. Because circulating levels of IL-6 and IL-6 soluble receptor (IL-6sR) are reportedly elevated in patients with hyperparathyroidism, we sought to determine whether measures of this cytokine axis could be helpful in determining the risk for bone loss in hyperparathyroidism. We prospectively followed 23 patients with hyperparathyroidism for 22 ± 1.5 months and found that baseline circulating levels of IL-6sR correlated significantly with rates of bone loss at the total femur (r = -0.53, P < 0.01). Furthermore, the combination of a serum IL-6sR in the upper tertile (45.6 ng/ml) and IL-6 in the upper half (11.8 pg/ml) of values in the whole group defined a subset of patients with a significantly greater rate of yearly bone loss at the total femur than the remainder of the group (-2.6 ± 1.3% vs. +0.4 ± 0.3%, P < 0.05). We conclude that the combined measurements of serum IL-6sR and IL-6 may be helpful in identifying patients with untreated hyperparathyroidism who are more likely to experience bone loss at the total femur.

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