Association between Increased Serum Osteoprotegerin Levels and Improvement in Bone Mineral Density after Parathyroidectomy in Hemodialysis Patients

Abstract

Secondary hyperparathyroidism (SHPT) is a common complication in chronic renal disease. Osteoprotegerin (OPG), an extracellular cytokine receptor secreted by osteoblasts, can promote bone formation by inhibiting the function of osteoclasts. Hemodialysis (HD) patients have elevated serum OPG levels. OPG secretion can be suppressed with high parathyroid hormone (PTH) levels. HD patients with refractory SHPT can benefit from parathyroidectomy (PTX) treatment, but the changes of serum OPG, bone turnover markers and bone mineral density (BMD) following PTX in HD patients remain unclear. In this study, patients on maintenance HD who received PTX for refractory SHPT (n = 28) were prospectively followed for 1 year. Serum intact PTH (iPTH), alkaline phosphatase (Alk-P), and OPG were measured serially; BMD was measured pre-PTX and at 1 year after PTX. After PTX, serum iPTH levels reduced profoundly. Serum Alk-P levels increased rapidly, peaking at 2 weeks post-PTX, while serum OPG levels gradually increased at 2 weeks after PTX and peaked at 2 months. BMD improved in both femoral neck (FN; cancellous and cortical bone) and lumbar spine (LS; cancellous bone). Higher baseline iPTH levels were associated with greater FN and LS BMD improvements at one year after PTX. The increment of serum OPG was correlated with the increase in LS BMD, implying that inhibition of osteoclastic bone resorption may improve BMD within the first year after PTX. These findings suggest that PTX removes the suppressive effects of high PTH on OPG secretion, resulting in the increased serum OPG levels that may contribute to BMD improvement.

Influence of Parathyroidectomy on Bone Metabolism and Bone Pain in Patients with Secondary Hyperparathyroidism

“…The preoperatively elevated OPG level of 10.9 ± 1 pmol/L in our study is in concordance with the findings reported by Zheng et al [47], who also observed elevated preoperative OPG levels in patients with sHPT. They observed increasing OPG levels within 2 weeks after PTX and explained this effect with the loss of the inhibiting effect of PTH [47].…”

“…They observed increasing OPG levels within 2 weeks after PTX and explained this effect with the loss of the inhibiting effect of PTH [47]. However, we observed no significant change perioperatively.…”

Serum Bone Resorption Markers after Parathyroidectomy for Renal Hyperparathyroidism: Correlation Analyses for the Cross-Linked N-telopeptide of Collagen I and Tartrate-Resistant Acid Phosphatase

“…The pathophysiology of the “hungry bone syndrome” observed after PTX is similar to the bone marrow ablation model used to investigate osteogenic capacity [10, 11]. Accordingly, PTX induces an initial rapid and prominent activation of bone synthetic activity, followed by a suppression of osteoclast activity which persists for at least one year [12]. …”

Calcitriol loading before total parathyroidectomy with autotransplant in patients with end‐stage kidney disease: does it prevent postoperative hypocalcaemia?

“…Continuously elevated PTH causes bone resorption and net bone loss . This is counteracted by a large increase in circulating osteoprotegerin which decreases osteoclast activation . The sudden drop in PTH after surgery leaves osteoprotegerin unopposed, inhibiting osteoclast activation and reducing bone resorption resulting in hypocalcaemia.…”

“…11 This is counteracted by a large increase in circulating osteoprotegerin which decreases osteoclast activation. 14 The sudden drop in PTH after surgery leaves osteoprotegerin unopposed, inhibiting osteoclast activation and reducing bone resorption resulting in hypocalcaemia. The significant difference in PTH between the groups may also reflect delays in parathyroidectomy and more severe hyperparathyroidism at the time of surgery.…”