Resolution of Effect of Bisphosphonates on Bone in Postmenopausal Osteoporosis

Participants of previous TRIO study - women who either received treatment with alendronate, ibandronate and risedronate for postmenopausal osteoporosis in secondary care. Control premenopausal women will also be recruited.

Inclusion Criteria:

Inclusion Criteria for postmenopausal women

• female be at least 7 years postmenopausal but less than 87 years of age
• be ambulatory
• be able and willing to participate in the study and provide written informed consent.
• have taken a bisphosphonate for 2 years as a participant in the TRIO study and be compliant > 80%
• have a Bone Mineral Density (BMD) T score > -2.5 at the femoral neck

Inclusion Criteria for premenopausal women

• be able and willing to participate in the study and provide written informed consent
• have previously taken part as premenopausal controls in the TRIO study
• be in good general health as determined by past medical and physical history
• be bisphosphonate naive; premenopausal women.

Exclusion Criteria:

Exclusion Criteria for postmenopausal women:

• An incident vertebral fracture or more than 5%/year bone loss at the spine or hip during the 2-year TRIO study
• Evidence of a clinically significant organic disease which could prevent the patient from completing the study, including diabetes
• Abuse of alcohol or use of illicit drugs or who consumed more than 4 units of any alcoholic beverage one day prior to the visit (i.e. subjects who might be binge drinkers)
• A history of cancer within the past 5 years excluding skin cancer non melanomas
• 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 Thyrotrophin-stimulating hormone (TSH) outside the lower limit of the normal range
• Hyperparathyroidism
• Hypocalcemia or hypercalcemia
• Osteomalacia
• Cushing's syndrome
• Current use of glucocorticoid therapy
• A serum calcium less than 2.2 mmol/l and a Parathyroid hormone (PTH) above 75ng/l
• A history of any known condition that would interfere with the assessment of Dual-emission X-ray absorptiometry (DXA) at either lumbar spine or femoral neck
• Markedly abnormal clinical laboratory parameters that are assessed as clinically significant by the principal investigator
• Require, in the opinion of the consulting physician, continuation of bisphosphonate therapy.

Exclusion Criteria for premenopausal women:

• Are pregnant or nursing (lactating)
• Use of any hormonal forms of contraception/ therapy within the past 2 years that would, in the opinion of the consulting physician, affect bone metabolism.
• Use of anabolic agents such as steroids or PTH, or any bisphosphonate within the past 2 years.
• Have any history of cancer within the past 5 years. Relatively benign skin malignancies, such as basal cell carcinoma or squamous cell carcinoma, are not an exclusion if the patient has been in remission for at least 6 months prior to enrolment.
• Have any chronic disease (HIV or AIDs, clinically significant renal or cardiovascular disease, hyperthyroidism, diabetes, hyperlipidemia) or menstrual cycle irregularity (by history)).
• Have any metabolic bone disease, such as osteoporosis, Paget 's disease, osteogenesis imperfecta, or serious illness affecting normal bone homeostasis (by history and physical exam if required)
• Significant use of any medications known to affect bone metabolism (such as Phenytoin or other anticonvulsants, Selective Estrogen Receptor Modulators (SERMs), heparin or systemic glucocorticosteroids) within the past 2 years.
• Have suffered a fracture within the last 12 months
• Have anorexia nervosa, suspected bulimia (by history or physical) or obvious malnutrition
• Have a history of alcoholism, or who have consumed more than 4 units of any alcoholic beverage one day prior to the visit (i.e., subjects who might be binge drinkers)
• Have previously participated in active therapy clinical trials within the last 3 months