Study of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease
Status:
Completed
Trial end date:
2009-09-01
Target enrollment:
Participant gender:
Summary
Cardiovascular disease (CVD) is the commonest cause of mortality in patients with chronic
kidney disease (CKD) and end-stage kidney disease (ESKD). Reasons for the greater incidence
of CVD in this group include traditional CVD risk factors of hypertension, dyslipidemia and
diabetes but more importantly also include non-traditional risk factors such as calcium and
phosphate imbalance. The latter is thought most likely to contribute to vascular
calcification, especially for those on dialysis, and this in turn leads to arterial stiffness
and left ventricular hypertrophy, the two commonest cardiovascular complications. Arterial
stiffness and calcification have been found to be independent predictors of all-cause and
cardiovascular mortality in CKD. Few studies, though, have looked at both structural and
functional changes associated with calcification and there have been very few interventional
studies addressing this issue.
Control of calcium and phosphate levels in CKD can occur with the use of medications that
reduce elevated serum phosphate (phosphate binders, mostly calcium-based) and those to treat
hyperparathyroidism (vitamin D and more recently calcium sensing receptor agonists called
calcimimetics). These pharmacological managements addressing calcium and phosphate imbalance
reduce vascular calcification and CVD. Bisphosphonate therapy may also have a role in
reduction of calcification.
Low bone mineral density (BMD) is common in CKD patients and predicts increased fracture risk
similar to the general population. Bisphosphonate therapy improves BMD and lowers the
fracture risk. Bisphosphonates may also have a role in secondary hyperparathyroidism to
reduce hypercalcemia and allow for more aggressive calcitriol treatment. Recent studies have
addressed the possibility of bisphosphonates reducing the progression of vascular
calcification in CKD and revealed that the extent of calcification may be suppressed in
association with a reduction in chronic inflammatory responses.
The investigators aim to perform a prospective, randomised study assessing the impact of
alendronate on cardiovascular and bone mineral parameters. This will be a single-centre study
involving subjects with CKD Stage 3 (those patients with GFR between 30 and 59ml/min).
Arterial stiffness (by pulse wave analysis and pulse wave velocity) and vascular
calcification (using CT scans through superficial femoral artery) will be followed as well as
serum markers of calcium, phosphate and PTH. Differences in these end-points will be compared
between participants taking alendronate and those not. The study will be conducted over a 12
month period and the investigators aim to recruit about 50 patients (25 on alendronate and 25
control).