Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomised Controlled Trial of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease: A Pilot Study
Brief 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).


Options:
A: Inclusion Criteria:

* Aged 21 years or older;
* Chronic maintenance dialysis of at least 3 months' duration;
* Osteoporotic by DXA of either spine or total hip (Women: post-menopausal or age ≥ 50 with T-score ≤ -2.5; Men: age ≥ 50 with T-score ≤ -2.5; All others, Z-score ≤ -2.5);
* Mental competence;
* Willingness to participate in the study;
* Normal serum calcium.

Exclusion Criteria:

* Pregnancy or breast feeding;
* Incarceration;
* Systemic illnesses or organ diseases that may affect bone (except type 1 or type 2 diabetes mellitus);
* Clinical condition that may limit study participation (e.g., unstable angina, respiratory distress, infections).
* Chronic alcoholism and/or drug addiction;
* Known Paget 's disease of bone;
* Prior external beam or implant radiation therapy involving the skeleton;
* More than 3 computed tomography (CT) scans in the prior 12 months (to avoid excessive radiation exposure);
* Participation in a study of an investigational drug during the past 90 days;
* Planning to move out of the area within 1 year of the study;
* On active transplant list;
* BMD t-score of the radius less than -3.5 by DXA (to avoid the known potential negative effects of teriparatide treatment on BMD of the radius);
* Planned or anticipated oral surgery within the next 12 months;
* Inability to stand or sit upright for at least 30 minutes;
* Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia;
* Treatment within last 6 months with drugs that may affect bone metabolism including bisphosphonates and teriparatide (except for treatment with calcitriol, vitamin D analogs and/or calcimimetics);
* Current treatment with medicines containing digoxin or warfarin;
* Calcidiol level below the normal range. (The current routine clinical practice in our dialysis clinics is to check calcidiol status twice yearly and supplement with vitamin D according to serum calcidiol levels. It is therefore unlikely that a substantial number of patients will be excluded due to this exclusion criterion.)
B: Inclusion Criteria:

1. Have received maintenance PD for more than 3 months at National Taiwan University Hospital,
2. Have high CPP level (≧50), and
3. Have chest X-ray proven aortic calcification or coronary artery calcification proven before.

Exclusion Criteria:

Patients are excluded if they have any one of the following conditions:

1. Had been hospitalized in recent 3 months due to severe comorbid diseases,
2. Are hypersensitive to alendronate or any of its components,
3. Have esophageal diseases
4. Are not able to stand or sit upright for 30 minutes,
5. Have refractory hypocalcemia, or
6. Patients who are pregnant.
C: Inclusion Criteria:

* Postmenopausal women with established coronary heart disease or at risk for a major coronary event.

Exclusion Criteria:

* Postmenopausal symptoms that required estrogen replacement therapy.
* Suspected or known history of breast or endometrial carcinoma.
* Known or probable history of deep venous thrombosis, pulmonary embolism, or retinal vein thrombosis.
* New York Heart Association classes III or IV heart failure.
D: Inclusion Criteria:

* Subjects with CKD Stage 3 (GFR between 30 and 59ml/min)
* Subjects must be 18 years of age or older
* Willingness to provide written informed consent

Exclusion Criteria:

* Subjects unable to give informed consent or whom have an expected life-span of less than 3 months
* Subjects undertaking renal replacement therapy (dialysis or transplantation)
* Subjects already taking bisphosphonates
* Subjects with recent fracture (within the last 3 months)
* Subjects scheduled to have a kidney transplant from a known living donor
* Subjects with active gastro-oesophageal reflux disease or peptic ulcer disease
* Subjects who are pregnant or planning on becoming pregnant in the next 18 months

Answer: D