Circulating RANKL is not a reliable biomarker for bone loss in primary hyperparathyroidism
Daniel Grigorie1,2, Alina Sucaliuc1,2, Elena Neacsu1, Roxana Militaru1, Alina Diaconescu1 & Mirela Ivan1
Introduction: The aim was to examine serum levels of RANKL, OPG and TNF-α before and after curative surgery (PTX) in patients with primary hyperparathyroidism, and their relationship to bone turnover and bone loss.
Patients and methods: A 46 patients with rather severe primary hyperparathyroidism (mean PTH=196 pg/ml, mean total Ca=11.4 mg/dl, spine osteoporosis in 50%, hip osteoporosis in a third) mean age of 63.3±12.3 years, 41 women/five males, had their serum RANKL, OPG and TNF-α measured at baseline and, in a subset, after curative surgery (25 patients, 14 paired data). Serum C-telopeptide (CTX) and osteocalcin, and BMD (spine and hip) were measured yearly.
Results: Baseline serum RANKL levels were extremely variable between subjects (1.1±1.7 pmol/l, range=0.046.24 pmol/l) and did not change after PTX. In patients having repeated measurements we noticed no difference in serum levels over time; a very good correlation between pre and post-surgery levels (r=0.99) was found. Circulating RANKL did not correlate with PTH but did correlate with serum CTX (r=0.36), serum osteocalcin (r=0.29) and with the annual change in BMD at the FN (%) (r=−0.44). Serum OPG levels (3.9±1.3 pmol/l) were in our normal postmenopausal range and did not change after PTX. We noticed a good correlation (r=−0.48) between serum RANKL:OPG ratio and the loss at FN. Serum TNF-α were extremely variable between subjects (29.35±48.94 pg/ml) but highly consistent in the same patient (r=0.99) and decreased non-significantly (P=0.08) after PTX. It correlated weakly with serum PTH (r=0.3), but not with either bone loss or CTX. There was a good correlation between serum CTX and femoral loss (r=−0.52).
Conclusion: Circulating levels of RANKL were extremely variable between subjects and did not change significantly after surgery. The rather weak correlation with serum CTX makes it unsuitable as a sensitive marker of bone loss.