Study of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease
Condition: Vascular Calcification; Arteriosclerosis
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Arteriosclerosis; Calcinosis; Vascular Calcification
Study type: Interventional
Phase: Phase 4

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).
    


Intervention name(s): Alendronate; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 70mg weekly orally; weekly orally
Other intervention name(s): Fosamax
Intervention MeSH terms: Alendronate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Vascular calcification; Arterial stiffness; Cardiovascular risk; Bone mineral metabolism; Calcium