Changes of bone turnover markers and serum PTH after night or morning administration of zoledronic acid in breast cancer patients with bone metastases

Abstract

Persistent circadian rhythm of bone turnover in bone metastatic breast cancer suggests greater skeletal retention of bisphosphonates if administered in the night. We assessed differential effects of night vs morning administration of zoledronic acid (ZA) on bone turnover. Forty-four breast cancer patients with bone metastases were randomised to receive intravenous ZA (4 mg) at 1100 or 2300 hours every 28 days for four times. Urinary concentration N-telopeptide of type-I collagen (NTX) and deoxypyridinolines, and serum C-telopeptide of type-I collagen (CTX), bone alkaline phosphatase (ALP), osteocalcin and Parathyroid hormone (PTH) was measured in the morning at baseline and after 4, 7, 14, 28, 56 and 84 days. Urinary ZA concentration was also measured. Zoledronic acid caused significant decreases of NTX and CTX (Po0.001), without any difference in percent changes between night and morning arms. Bone ALP and osteocalcin were also significantly affected by ZA (P ¼ 0.001), without any difference between arms. Parathyroid hormone significantly increased in both the arms; PTH increase was lower in the night arm (P ¼ 0.001). From the second administration onwards, urinary ZA level was significantly higher in the night arm (Po0.01). Administration of ZA at two opposite phases of the circadian cycle causes similar changes of bone-turnover marker levels, but has differential effects on the level of serum PTH.

Frequency of Bone Metastases with Metabolic Super Scan in Cancer Breast Patients

“…On the other hand similar values for calcium and parathyroid hormone were recorded for both MSS and Non-MSS groups with no significant difference in-between. These results disagree with other authors [7,26] who demonstrate elevated PTH and serum calcium levels in MSS compared to Non-MSS patients. This discrepancy may be attributed to different pathophysiological mechanism for MSS as well as variation in duration and different population of the study.…”

“…Biochemical markers are usually used to provide information regarding the changes occurring in bone metabolism especially osteoclastic activity [7] . Multiple limitations have been addressed by many authors that interfere with wide acceptance for their use in clinical practice.…”

“…These include availability, cost, technical demands, multiplicity as well as lack of specificity and standardization. In addition, these laboratory assays suffer from cross reactivity, difference in immunoassays and are influenced by gender, age, diurnal variation as well as liver diseases [7,8,9,10,11] .…”

Severe Refractory Hypocalcemia in a Patient with Metastatic Prostate Carcinoma Following Denosumab Injection

“…This may have been related to higher PTH levels which can occur after Zoledronic acid administration. Higher baseline PTH levels in these patients may prevent severe drop in calcium levels after Denosumab therapy [16]. In a recent study, serum alkaline phosphatase was found to be an independent risk factor, especially if the baseline level was greater than 500 IU/l.…”

Identification of the Risk Factors Associated with Hypocalcemia Induced by Denosumab

“…19) It is known that the secretion of PTH is increased after administration of zoledronic acid and the increases of PTH concentration are continued for about 1-2 months. 3,20,21) In this study, denosumab was administered within 2 months after administration of zoledronic acid in the zoledronic acid pretreatment group. Therefore, we considered that the PTH concentration in the patients of the zoledronic acid pretreatment group were likely increased.…”