Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture.²⁵ Bone strength is based on bone density and other factors, such as remodeling frequency (bone turnover), bone size and area, bone microarchitecture and degree of bone mineralization. While there is a strong inverse relationship between BMD and fracture risk, the rate of bone turnover is also a risk factor for fracture. Cancellous/trabecular bone is more sensitive to high bone turnover. Rapid bone turnover can disrupt the underlying microarchitecture of bone thus affecting bone strength. Because new bone synthesis is a slower process than bone resorption, rapid bone turnover can lead to an imbalance in bone renewal and to loss of connectivity within the trabeculae. Loss of connectivity irreversibly weakens the structural integrity of the bone and is a more serious consequence than mere thinning of the trabeculae. Such a weakening of bone microarchitecture has been found in early postmenopausal women. Since the relationship between changes in BMD and antifracture benefit with antiresorptive therapies is neither linear nor proportional, there has been interest in studying the effect of antiresorptive agents on bone microarchitecture as a way of more fully explaining their antifracture effect. While the biochemical products of bone turnover are often measured in clinical trials of osteoporosis therapies, at the present time the exact clinical role of biochemical turnover markers has not been established.¹⁶