Skeletal deposition of clodronate is related to parathyroid function and bone turnover in dialysis patients

Bisphosphonates inhibit osteoclastic bone resorption, and in the future, they may also have a role in the therapy of renal osteodystrophy. Our aim was to study whether the severity of hyperparathyroidism has an effect on the clearance of clodronate via routes other than dialysis or kidneys (nonrenal, non-dialysis clearance, CL(NRD)), which most likely represents the deposition of the drug in the skeleton.

We studied 31 dialysis patients (9 female/22 male, aged 28 - 79, median 58 years), 18 on hemodialyis (HD) and 13 on peritoneal dialysis (PD). HD patients were studied on a non-dialysis day. An intravenous infusion of 300 mg clodronate was given during 60 min at 8:00 a.m. Blood, urine and PD fluid samples were collected for 1 + 24 h, and pharmacokinetic parameters were calculated.

In PD patients, 7% of the infused drug was excreted into PD fluid within 24 h, and in those HD or PD patients with residual diuresis 11% was excreted via the kidneys. The highest CL(NRD) was seen in patients with the most severe hyperparathyroidism. There was a positive correlation between CL(NRD) and plasma intact PTH (r = 0.79, p < 0.001). CL(NRD) was also related to the serum levels of bone markers PINP (procollagen type I N-terminal propeptide, r = 0.81, p < 0.001), osteocalcin (r = 0.65, p < 0.001) and ICTP (type I collagen cross-linked telopeptide, r = 0.68, p < 0.001). However, even in the patients with normal PTH, more than one-third of the infused drug was taken up by bone.

In dialysis patients, the skeletal deposition of clodronate is related to bone turnover being highest in severe hyperparathyroidism. However, even in the case of low turnover, the uptake of the drug in bone takes place in amounts that might be clinically significant.