Condition category
Musculoskeletal Diseases
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Prof David M Reid


Contact details

Division of Applied Medicine
Medical School
University of Aberdeen
AB24 1FX
United Kingdom
+44 1224 51154

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title


Study hypothesis

That co-treatment of patients receiving potent nitrogen containing bisphosphonates (N-BP), with a statin, would prevent the activation and increase in gamma,delta-T cells and therefore prevent the subsequent acute phase response that occurs after the infusion of the N-BP.

Ethics approval

Grampian Local Research Ethics Committee. Date of approval: 24/03/2005 (ref: 05/S0801/39)

Study design

Single-centre, randomised controlled trial.

Primary study design


Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Osteopenia/ osteoporosis


The participants will be randomly allocated to the following three arms:

Arm 1: Oral fluvastatin (40 mg immediate release formulation) immediately prior to an intravenous (iv) infusion of zoledronic acid (5 mg) + an oral dose placebo fluvastatin on the 1st and 2nd day after the infusion.

Arm 2: Single dose of matching placebo fluvastatin, immediately prior to an infusion of zoledronic acid (5 mg) and an oral dose placebo fluvastatin on the 1st and 2nd day after the infusion.

Arm 3: Oral dose of fluvastatin (40 mg immediate release formulation) immediately prior to an iv infusion of zoledronic acid (5 mg) + an oral dose of fluvastatin on the 1st and 2nd day after the bisphosphonate infusion.

Intervention type



Not Specified

Drug names

Bisphosphonates, zoledronic acid and fluvastatin.

Primary outcome measures

Serum C reactive protein (CRP) at 72 hours.

Secondary outcome measures

1. Changes in cytokines (tumour necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6] and interferon gamma) at 24 hours
2. Changes in serum cholesterol at 48 hours
3. Alterations in temperature post infusion (at 24 hours)
4. Alterations in acute phase response as assessed by questionnaire at 72 hours

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Postmenopausal women over the age of 20 and more than 12 months after cessation of menses or with serum estradiol and/or follicle stimulating hormone (FSH) levels consistent with a post-menopausal state, but <= 10 years post menopause
2. Bisphosphonate naïve women with osteopenia as defined by the World Health Organization (WHO) (T-score <= 1.0 but >-2.5) or osteoporosis as defined by the WHO (T-score <-2.5) at the lumbar spine or total hip Bone Mineral Density (BMD) measurement sites
3. Women willing and able to give informed consent

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. The patient has a history of hypersensitivity to any statin or previously exposed to fluvastatin
2. The patient has a history of any illness or has significant abnormalities on pre-study clinical or laboratory evaluation which, in the opinion of the investigator, might either pose an unacceptable risk to the patient from participation in this study or complicate the interpretation of study data
3. The patient is a current user of any illicit drugs or has a history of drug or alcohol abuse within the past five years
4. The patient has a history of or evidence for metabolic bone disease (other than postmenopausal bone loss) including but not limited to vitamin D deficiency, hypoparathyroidism, primary hyperparathyroidism, recent hyperthyroidism (suppressed thyroid stimulating hormone [TSH] within the six months prior to entry into the study), Paget's disease of bone, osteomalacia or renal osteodystrophy
5. The patient has any other disease potentially associated with increased bone turnover including, but not exclusive to, rheumatoid arthritis, Crohn's disease, severe renal impairment or severe hepatic disease
6. The patient has a history of cancer except for the following:
6.1. Superficial basal or squamous cell carcinoma of the skin which has been completely resected
6.2. Stage I breast cancer (lesion <= 3 cm with no nodal or local invasion) which has been completely treated more than one year ago with no evidence of recurrence
6.3. Other malignancies completely treated without recurrence or treatment in the last 5 years
7. Baseline renal insufficiency defined as either baseline creatinine of >177 mmol/l and/or calculated creatinine clearance of < 40ml/min
8. Serum 25-OH vitamin D level <15 ng/ml
9. Serum calcium <2 mmol/L and >2.75 mmol/L
10. Serum alkaline phosphatase >1.5x Upper Limit of Normal (ULN) and/or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 x ULN
11. The patient is receiving or has received treatment prior to randomisation which might influence bone turnover, including:
11.1. Any treatment with parathyroid hormone during the year prior to randomisation
11.2. Within the last 6 months: oestrogen, oestrogen analogues (e.g., raloxifene, tamoxifen), tibolone or anabolic steroids. Oestrogen taken >3 months ago for <= 1 week is acceptable. Topical (vaginal) oestrogen cream (<= 2 g) used up to two times weekly is acceptable
11.3. Thyroid hormone, unless on a stable dose for at least six weeks before randomisation with serum TSH within the normal range; patients found at screening to have mild hypothyroidism (as indicated by an elevation in TSH to no more than 15 µIU/ml) are eligible to enter the study provided they receive careful thyroid replacement therapy, if needed, and TSH levels are monitored three months later and as appropriate during the study
11.4. Glucocorticoid treatment for more than one month with >7.5 mg of oral prednisone (or the equivalent) per day within six months prior to randomisation; high-dose, intravenously within 6 months prior to randomisation; patients who have received therapeutic glucocorticoids in the past must be considered highly unlikely to require retreatment (with >7.5 mg of oral prednisone daily or the equivalent for more than one month or <= 500 mg of methylprednisolone pulse at any time) during the course of the study
12. Treatment with an immunosuppressant (e.g., cyclosporine, azathioprine) within the previous year
13. The patient is receiving or is expected to receive during the course of the study any medication (other than study medication) that might alter bone or calcium metabolism, including vitamin D in excess of 5000 IU per day, calcitonin, phenytoin, heparin, or lithium
14. HIV patients
15. No History of uveitis, iritis or conjunctivitis
16. No history of retinopathy or nephropathy especially in the presence of uncontrollable insulin dependent diabetes mellitus HB1AC >10%.
17. Any patient with severe dental problems or current dental infections, or with recent or pending surgery within 3 months of dosing

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Division of Applied Medicine
AB24 1FX
United Kingdom

Sponsor information


University of Aberdeen (UK)

Sponsor details

c/o Mr Fred Stevenson-Robb
Research & Innovation
Regent Walk
AB24 1FX
United Kingdom

Sponsor type




Funder type


Funder name

Novartis Pharmaceuticals (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2010results in

Publication citations

  1. Thompson K, Keech F, McLernon DJ, Vinod K, May RJ, Simpson WG, Rogers MJ, Reid DM, Fluvastatin does not prevent the acute-phase response to intravenous zoledronic acid in post-menopausal women., Bone, 2011, 49, 1, 140-145, doi: 10.1016/j.bone.2010.10.177.

Additional files

Editorial Notes