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Notes: Abstract: Cardiac transplantation exposes recipients to osteoporosis and increased risk of consequent fractures. The purpose of the present study was to examine the magnitude, timing and mechanism of bone loss following cardiac transplantation, and to establish whether bone loss can be prevented by calcium with or without calcitonin. Thirty patients (29 men, 1 woman), aged 26 – 68 years (mean 48 years), were randomized into three groups of 10 to receive either no additional treatment, oral calcium 1 g twice daily for 12 months or the same dose of calcium plus intranasal calcitonin 400 IU/day for the first month and then 200 IU/day for 11 months. Bone mineral density (BMD) at the lumbar spine and three femoral sites (femoral neck, trochanter, Ward’s triangle) was measured by dual-energy X-ray absorptiometry (DXA) at the time of transplantation and 6 and 12 months later. Markers of bone formation [serum bone-specific alkaline phosphatase (B-ALP), type I procollagen carboxyterminal propeptide (PICP) and aminoterminal propeptide (PINP)] and resorption [serum type I collagen carboxyterminal telopeptide (ICTP)], as well as serum testosterone in men, were assayed before transplantation and at 1 week and 1, 3, 6 and 12 months after transplantation. During the first 6 post-transplant months BMD calculated as a percent change from baseline decreased in the control group by 6.4% (p= 0.014) in the lumbar spine, by 6.0% (p= 0.003) in the femoral neck, by 5.0% (p= 0.003) in the trochanter and by 5.5% (p= 0.130) in Ward’s triangle. Between 6 and 12 months a further decline in BMD occurred only at the three femoral sites, ranging from 2.2% to 9.8% (p= 0.004-0.079). In comparison with the control group, the group receiving calcium alone lost less bone in the trochanter between 0 and 6 months (p= 0.019), and the group receiving calcium together with calcitonin lost less bone in the femoral neck (p= 0.068) and Ward´s triangle (p= 0.076) between 0 and 12 months. Seven (28%) of 25 assessable patients experienced vertebral compression fractures. Calcium with or without calcitonin had no effect on changes in biochemical parameters; consequently, the three study groups were combined. The markers of bone formation increased, the elevations in mean values being 59% for B-ALP at 1 month (p= 0.009), 152% for PICP at 1 week (p 〈 0.0001) and 27% for PINP at 1 week (p= 0.021). After a temporary decline at 3 months B-ALP (p= 0.0002) and PINP (p 〈 0.0001) at 1 year were nearly doubled compared with baseline values. Throughout the study the marker of bone resorption, serum ICTP, was above normal, with a peak (mean values 67–69% above baseline) at 1 week (p= 0.0002) to 1 month (p 〈 0.0001). The mean concentration of total testosterone was decreased by 48% (p 〈 0.0001) 1 week and by 28% (p= 0.0005) 1 month after transplantation, but this was mainly explained by the concomitant drop in serum albumin. High bone turnover underlies bone loss after cardiac transplantation. Bone loss is most rapid during the first 6 post-transplant months. In the upper femur this bone loss may be reduced by treatment with calcium and calcitonin.

Notes: Abstract. 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.

Notes: Abstract Objective: The effect of food on the bioavailability of oxybutynin was assessed in a randomised cross-over study in 23 healthy volunteers. A single oral 10 mg dose of a controlled release oxybutynin tablet was administered after a high fat breakfast and to fasting subjects. The AUC, Cmax, tmax, t1/2 and MRT of oxybutynin and its active metabolite N-desethyloxybutynin were determined. Results: Breakfast did not change the AUC of oxybutynin but increased the AUC of N-desethyloxybutynin by about 20% . The Cmax of oxybutynin and N-desethyl oxybutynin were two-fold higher when the drug was administered after breakfast compared to the fasting state. Conclusion: Breakfast significantly reduced the MRT of oxybutynin and N-desethyloxybutynin.