The role of the receptor activator of nuclear factor-kappaB ligand/osteoprotegerin cytokine system in primary hyperparathyroidism.
BACKGROUND
The mechanisms of action of PTH on bone in vivo remain incompletely understood. The objective of this investigation was to examine changes in serum levels of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin (OPG) in primary hyperparathyroidism and their relationship to bone loss.


METHODS
Twenty-nine patients with primary hyperparathyroidism had baseline circulating soluble receptor activator of nuclear factor-kappaB ligand (sRANKL) and OPG measured. The relationship to biochemical markers of bone turnover and changes in bone mineral density over 2 yr was examined.


RESULTS
Baseline sRANKL levels were elevated (1.7+/-0.1 pmol/liter), whereas OPG remained in the normal range (5.6+/-0.4 pmol/liter). Circulating sRANKL did not correlate with PTH but did correlate with markers of bone resorption (urine deoxypyridinoline cross-links: r=0.51, P<0.01; serum N-telopeptide of type I collagen: r=0.37, P<0.05). Furthermore, sRANKL correlated with both IL-6 and IL-6 soluble receptor (IL-6sR) (r=0.47, P<0.05 and r=0.55, P<0.005, respectively). Serum sRANKL levels also correlated with bone loss at the total femur (r=-0.53, P<0.01). Lastly, a high value of sRANKL in combination with values of IL-6 and IL-6sR in the upper quartile (sRANKL>or=1.81 pg/ml, IL -6>or=11.8 pg/ml, and IL-6sR>or=45.6 ng/ml) defined a group of four women with significantly greater rates of bone loss at the total femur than the remaining patients (-2.7+/-1.7% vs. +0.5+/-0.3%; n=4 vs. n=19, P<0.05).


CONCLUSIONS
Determination of circulating levels of sRANKL may be useful in identifying patients with mild primary hyperparathyroidism at greater risk for bone loss. The fact that circulating sRANKL did not correlate with PTH but did correlate with markers of bone resorption suggests that skeletal responsiveness to PTH may differ in this disease.
Nakchbandi
Inaam A
IA
Department of Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. inaam.nakchbandi@urz.uni-heidelberg.de
Lang
Robert
R
Kinder
Barbara
B
Insogna
Karl L
KL
D000368:Aged; D015519:Bone Density; D016723:Bone Remodeling; D005260:Female; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000209:etiology*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood / Q000502:physiology*; D010281:Parathyroid Hormone / Q000097:blood; D053245:RANK Ligand / Q000097:blood / Q000502:physiology*; D019947:Receptors, Interleukin-6 / Q000097:blood
D015850:Interleukin-6; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; D019947:Receptors, Interleukin-6; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human