Role of the interleukin-6/interleukin-6 soluble receptor cytokine system in mediating increased skeletal sensitivity to parathyroid hormone in perimenopausal women

J Bone Miner Res. 2002 Nov:17 Suppl 2:N108-16.

Abstract

We have observed a strong correlation between circulating levels of both interleukin-6 (IL-6) and interleukin-6 soluble receptor (IL-6sR) and rates of bone turnover in patients with primary hyperparathyroidism. Furthermore, we have found that serum levels of IL-6sR predict rates of bone loss in postmenopausal women with this disease. Estrogen modulates parathyroid hormone (PTH)-induced increases in serum IL-6/IL-6sR, such that, in the estrogen-deficient state, there is an exaggerated release of these cytokines. We therefore propose that the perimenopausal period represents a time when skeletal sensitivity to the resorbing actions of PTH increases because of augmented release of IL-6 and IL-6sR. To test this hypothesis, we retrospectively examined data from 91 women with primary hyperparathyroidism who were seen over the last 5 years at our institution. Women were categorized, based on their age, as premenopausal (n = 20, 41 +/- 2 years), perimenopausal (n = 17, 54 +/- 1 years), or postmenopausal (n = 54, 64 +/- 1 years). Despite having similar mean values for PTH, perimenopausal women had a mean serum IL-6 value that was significantly higher than that in the premenopausal group (13 +/- 2 vs. 8 +/- 2 pg/ml; p = 0.03). This difference in cytokine profile was mirrored by higher mean values for urine N telopeptides of type I collagen (NTX) in the perimenopausal group compared with premenopausal women (114 +/- 9 vs. 80 +/- 11 nM bone collagen equivalents (BCE)/mM creatinine, p = 0.01). Of the three groups of patients, values for IL-6 and urine NTX were highest in the postmenopausal group. We conclude that the perimenopausal period may be a time of increased risk for the skeletal complications of hyperparathyroidism. This is because of increased skeletal sensitivity to the resorbing actions of PTH, mediated in part, by the IL-6/IL-6sR cytokine system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Bone Resorption / metabolism
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism*
  • Collagen / urine
  • Collagen Type I
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Estrogens / deficiency
  • Estrogens / physiology
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperparathyroidism / complications
  • Hyperparathyroidism / metabolism
  • Interleukin-6 / blood
  • Interleukin-6 / physiology*
  • Menopause / metabolism
  • Mice
  • Middle Aged
  • Osteoporosis, Postmenopausal / complications
  • Osteoporosis, Postmenopausal / metabolism
  • Parathyroid Hormone / blood
  • Parathyroid Hormone / pharmacology
  • Parathyroid Hormone / physiology*
  • Peptides / urine
  • Postmenopause / metabolism
  • Predictive Value of Tests
  • Premenopause / metabolism
  • Receptors, Interleukin-6 / drug effects
  • Receptors, Interleukin-6 / physiology*
  • Reference Values
  • Retrospective Studies

Substances

  • Collagen Type I
  • Cytokines
  • Estrogens
  • Interleukin-6
  • Parathyroid Hormone
  • Peptides
  • Receptors, Interleukin-6
  • collagen type I trimeric cross-linked peptide
  • Collagen