Osteoprotegerin Serum Levels in Primary Hyperparathyroidism and Changes Following Surgery

Dear Editor,

We enjoyed reading the paper by Szymczak and Bohdanowicz-Pawlak [1], addressing the role of osteoprotegerin (OPG), receptor activator of nuclear factor κB (RANK), and its ligand (RANKL) in patients with primary hyperparathyroidism, and the differential effects of surgery and bisphosphonate treatment.

We were particularly fascinated by the basal levels and the absence of changes following parathyroidectomy of serum osteoprotegerin values. These results are, for example, in contrast to the changes observed following parathyroid hormone (PTH) treatment [2] of postmenopausal patients with glucocorticoid-induced osteoporosis; indeed, Buxton and co-workers [2] found a PTH-induced upregulation of osteoblast cytokines such as RANKL, IL-6, and IL-6sR, but a suppression of OPG, following human PTH 1–34 treatment.

One possible explanation for the findings observed one year after parathyroidectomy could be the fact that there is still an increased pool of osteoblasts or osteoblast precursor cells, which produce OPG. This seems to be supported by the continuous increase of BMD, as we have also previously demonstrated. In this respect, it would be important to know if the authors found any correlations between early [3] and late [4] changes of markers of bone turnover and the single components of the OPG/RANK/RANKL axis.

Finally, another important observation is the peculiarity of patients studied, which seems to be characterized by an important bone involvement nowadays no more commonly observed. It could be interesting to know the vitamin D levels of these patients, which have been advocated to influence clinical manifestation of the disease [5] and how this could impact on the time course of the markers studied. Lastly, a word of caution should be offered because there is the possibility that the assay commonly utilized for measuring OPG is far from being perfect and/or cannot reflect what is going on at the skeletal level.

• References

• 1 Szymczak J, Bohdanowicz-Pawlak A. Osteoprotegerin, RANKL, and bone turnover in primary hyperparathyroidism: the effect of parathyroidectomy and treatment with alendronate. Horm Metab Res 2013; 45: 759-764
• 2 Buxton EC, Yao W, Lane NE. Changes in serum receptor activator of nuclear factor-κB ligand, osteoprotegerin, and interleukin-6 levels in patients with glucocorticoid-induced osteoporosis treated with human parathyroid hormone (1–34). J Clin Endocrinol Metab 2004; 89: 3332-3336
• 3 Minisola S, Romagnoli E, Scarnecchia L, Rosso R, Pacitti MT, Scarda A, Mazzuoli G. Serum carboxy-terminal propeptide of human type I procollagen in patients with primary hyperparathyroidism: studies in basal conditions and after parathyroid surgery. Eur J Endocrinol 1994; 130: 587-591
• 4 Guo C-Y, Thomas WEG, Al-Dehami AW, Assiri AMA, Eastell R. Longitudinal changes in bone mineral density and bone turnover in postmenopausal women with primary hyperparathyroidism. J Clin Endocrinol Metab 1996; 81: 3487-3491
• 5 Carnevale V, Manfredi G, Romagnoli E, De Geronimo S, Paglia F, Pepe J, Scillitani A, D’Erasmo E, Minisola S. Vitamin D status in female patients with primary hyperparathyroidism: does it play a role in skeletal damage?. Clin Endocrinol (Oxf) 2004; 60: 81-86