EFFECTS OF SHORT-TERM TREATMENT WITH CLODRONATE ON PARAMETERS OF BONEMETABOLISM AND THEIR DIURNAL-VARIATION

The goal of the present study was to answer the question whether the d iurnal variation of markers of bone turnover is abolished by inhibitio n of osteoclasts by bisphosphonates and to assess the effects of short -term treatment with clodronate on parameters of calcium and bone meta bolism. Nine healthy, postmenopausal women, all aged 68 years, were st udied 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 meal s and were recumbent from 10:00 P.M. to 6:00 A.M. Blood was sampled ev ery 2 hours and urine was collected in 4-hour aliquots. On each study occasion, three markers of bone resorption (ICTP, serum type-I collage n carboxyterminal telopeptide; F-Pyr, urinary-free pyridinoline; and N Tx, crosslinked N-telopeptide of type I collagen) and one marker of bo ne formation (PICP, serum type I procollagen carboxyterminal propeptid e) showed a diurnal variation; only that of NTx was lessened by treatm ent with clodronate. Mean area under curve (AUG) values for the 24-hou r 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 = 0.4 1) and PICP (P = 0.99). Treatment with clodronate decreased mean AUC f or the serum concentration of total calcium by 1.4% (P = 0.030) and th at for the urinary excretion of calcium by 33% (P = 0.021). Mean AUC f or serum-intact PTH increased by 19% (P = 0.004). We conclude that sho rt-term treatment with clodronate lowers serum and urine calcium level and causes compensatory hyperparathyroidism. Treatment also clearly d ecreases the urinary excretion of NTx and lessens its diurnal variatio n. As assessed by sensitive markers such as NTx, the nocturnal rise in bone resorption is greatly blunted by inhibition of osteoclasts with bisphosphonates.