Effects of short-term treatment with clodronate on parameters of bone metabolism and their diurnal variation

The goal of the present study was to answer the question whether the diurnal variation of markers of bone turnover is abolished by inhibition of osteoclasts by bisphosphonates and to assess the effects of short-term treatment with clodronate on parameters of calcium and bone metabolism. Nine healthy, postmenopausal women, all aged 68 years, were studied before and after oral administration of clodronate, first 800 mg daily for 2 weeks and then 1600 mg daily for 2 weeks. During the two-study sessions of 24 hours, the subjects received exactly similar meals and were recumbent from 10:00 P.M. to 6:00 A.M. Blood was sampled every 2 hours and urine was collected in 4-hour aliquots. On each study occasion, three markers of bone resorption (ICTP, serum type-I collagen carboxyterminal telopeptide; F-Pyr, urinary-free pyridinoline; and NTx, crosslinked N-telopeptide of type I collagen) and one marker of bone formation (PICP, serum type I procollagen carboxyterminal propeptide) showed a diurnal variation; only that of NTx was lessened by treatment with clodronate. Mean area under curve (AUC) values for the 24-hour study periods decreased by 41% (P = 0.0002) and 4.7% (P = 0.016) for urinary NTx and F-Pyr, but remained unchanged for serum ICTP (P = 0.41) and PICP (P = 0.99). Treatment with clodronate decreased mean AUC for the serum concentration of total calcium by 1.4% (P = 0.030) and that for the urinary excretion of calcium by 33% (P = 0.021). Mean AUC for serum-intact PTH increased by 19% (P = 0.004). We conclude that short-term treatment with clodronate lowers serum and urine calcium levels and causes compensatory hyperparathyroidism. Treatment also clearly decreases the urinary excretion of NTx and lessens its diurnal variation. As assessed by sensitive markers such as NTx, the nocturnal rise in bone resorption is greatly blunted by inhibition of osteoclasts with bisphosphonates.