Implanted bisphosphonates in bone cement affect bone markers in rat serum

Abstract

Purpose: Bisphosphonates (BPs) are antiresorptive drugs that provide important effects on bone turnover. The key to the high efficiency of BPs is their affinity for bone tissue, and their chemical structure provides their molecular mechanism of action. BPs are widely used to treat a variety of diseases that cause excess bone resorption, such as bone metastasis, hypercalcaemia due to malignancy and Paget's disease. The goal of this study was to assess whether the bisphosphonate (Pamifos®) present in bone cement has any effect on bone turnover. In this paper, we present changes in cytokine levels in the serum of rats treated surgically.

Methods: Research was performed on 40 adult male Wistar rats. The rats were divided into four groups: two control groups (A, B) and two experimental groups (C, D). Bone in rats in the experimental groups was implanted with BP-enriched cement, whereas bone in control-groups rats was implanted with clean cement (without BPs).

Results: We found a higher concentration of tumour necrosis factor alpha (TNF-α) three weeks after surgery in rats implanted with BP-enriched cement compared with rats implanted with clean cement. After six weeks of treatment, TNF-α levels decreased significantly in rats treated with BP-enriched cement, whereas the control group experienced an increase in TNF-α. The concentration of osteoprotegerin ligand (OPG) was higher in rats with BP implants. We found high levels of receptor activator of nuclear factor kappa-B ligand (RANKL) in rats after implantation of cement without BP in both groups.

Conclusions: We conclude that use of bisphosphonate (Pamifos®), which is present in bone cement, has an effect on bone turnover in that BPs stimulate an increase in OPG and a decrease in RANKL in the bone microenvironment and thus may be an important component of mechanisms that reduce bone resorption. Therefore, the use of BP-enriched cement implants appears to be justified.

Fig. 1

Median level of tumour necrosis factor alpha (TNF-α) concentration in rats’ serum after clean cement was implanted into the bone (a, b) in comparison with rats implanted with bisphosphonate (BP)-enriched cement (c, d)

Fig. 2

Median level of osteoprotegerin (OPG) concentration in rats’ serum after bone implantation with clean cement (a, b) in comparison with rats implanted with bisphosphonate (BP)-enriched cement (c, d)

Fig. 3

Median level of receptor activator of nuclear factor kappa-B ligand (RANKL) concentration in rats’ serum after bone implantation with clean cement (a, b) in comparison with rats implanted with bisphosphonate (BP)-enriched cement (c, d)