Bisphosphonate Action on the Appendicular Skeleton: Evidence for Differential Effects

• Status: Completed
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: Female

Summary

A study to determine if the three licensed bisphosphonates (alendronate, ibandronate and risedronate):a) affect the peripheral skeleton differently, as assessed by quantitative ultrasound of bone (QUS), peripheral quantitative computed tomography (pQCT) and dual-energy x-ray absorptiometry (DXA)? b) have different effects on bone cells and their activity as assessed by flow cytometry and biochemical markers of bone cell activity? The aim of the study is to compare the effects of three licensed bisphosphonates on bone quantity and quality. There has been no such study before. Most of the measures of bone quantity and quality used in this protocol have not been studied with any of these three agents. The novelty of the study necessitates the establishment of reference ranges and this explains the need for the inclusion of a group of young women.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
• Collaborators: Procter and Gamble; University of Sheffield
• Treatments: Alendronate; Diphosphonates; Etidronic Acid; Ibandronic Acid; Risedronate Sodium; Risedronic Acid

Criteria

Inclusion Criteria:

• be female

• at least 5 years post menopausal but <85 years

• BMD T-score (at the lumbar spine or total hip) of less than or equal to

• 2.5, or T-score less than or equal to -1 with a low trauma fracture.

• be ambulatory

• be able and willing to participate in the study and provide written informed consent

Exclusion Criteria:

• have evidence of a clinically significant organic disease which could prevent the patient from completing the study

• have a BMI less than 18 or greater than 35

• abuse alcohol or use illicit drugs or who consumed more than 4 servings of any alcoholic beverage one day prior to the visit (i.e., subjects who might be binge drinkers)

• have any history of cancer within the past 5 years excluding skin cancer non melanomas

• have a history of ongoing conditions or diseases known to cause abnormalities of calcium metabolism or skeletal health (secondary osteoporosis)

• Chronic renal disease (as defined by a creatinine clearance of ≤ 30ml/min)

• Acute or chronic hepatic disease

• Malabsorption syndromes

• Hyperthyroidism as manifested by TSH outside the lower limit of the normal range

• Hyperparathyroidism

• Hypocalcemia or hypercalcemia

• Osteomalacia

• Cushing's syndrome

• Patient who are currently on glucocorticoid therapy

• have a serum calcium less than 2.2 mmol/l and a PTH above 75ng/l

• have a history of any known condition that would interfere with the assessment of DXA at either lumbar spine or femoral neck

• have markedly abnormal clinical laboratory parameters that are assessed as clinically significant by the investigator

• use any of the following medications within 12 months of starting study drug

• Bisphosphonates (at any dose)

• Use of any fluoride with the exception use for oral hygiene

• Strontium

• Other bone agents (i.e., SERM, isoflavones, HRT etc)

• have participated in another clinical trial involving active therapy 3 months prior to randomisation

• have a history of allergic reaction to bisphosphonates

• patient taking calcium supplements within the last month prior to randomisation

• We will exclude patients with secondary osteoporosis, those who have been on anti-resorptive treatments in the past year, and women less than 5 years since menopause, and those with bilateral fractures in the measurement regions (heel, hip and forearm).

• Have suffered a recent fracture within the last 12 months