Disorders associated with acute rapid and severe bone loss.

We describe a constellation of bone diseases characterized by the common feature of acute, rapid, and severe bone loss accompanied by dramatic fracture rates. These disorders are poorly recognized, resulting mainly from systemic diseases, frailty, immobilization, and immunosuppressive drugs, such as glucocorticoids and the calcineurin inhibitors. The opportunity to prevent or treat fractures is commonly missed because they are often not detected. Ideally, patients need to be identified early and preventative therapy initiated promptly to avoid the rapid bone loss and fractures. The most effective therapy at present seems to be the bisphosphonates, particularly when bone resorption is predominant. However, more severe forms of bone loss that result from an osteoblastic defect and reduced bone formation may benefit potentially more from newer anabolic agents, such as recombinant human parathyroid hormone (rhPTH).

Calcitonin: the other thyroid hormone.

Calcitonin was originally discovered as a hypocalcemic factor synthesized by thyroid parafollicular C cells. Early experiments demonstrated that calcitonin inhibited bone resorption and decreased calcium efflux from isolated cat tibiae and subsequent histologic and culture studies confirmed the osteoclast as its major site of action. Its potent antiresorptive effect and analgesic action have led to its clinical use in treatment of Paget's bone disease, osteoporosis, and hypercalcemia of malignancy. This review surveys the cellular and molecular basis of these physiologic and clinical actions.

Osteoporosis: trends and intervention.

Osteoporosis is a skeletal disorder in which bone strength is compromised due to loss of bone density and bone quality. It is the leading cause of serious morbidity and functional loss in the elderly. At times, it is difficult for the clinician to distinguish between the disease and normal skeletal aging, but advances in the scientific understanding of the underlying disease process have made management of osteoporosis a preventable disease for the most part. Defining the point at which these age-related skeletal changes require intervention presents a major challenge to researchers and clinicians alike. There are several reasons for these difficulties. There is a long period of bone loss before the onset of clinically apparent disease. Also current diagnostic procedures have been shown to distinguish those at risk of fracture and those not at risk, there is a large overlap in bone density between persons who experience fractures and those who do not. Research efforts directed at these issues have increased dramatically, as have developing technologies in the measurement and screening of bone mineral density. Ongoing advances in the therapeutic modalities have promoted new methods to treat this disorder. The foregoing review will describe the mechanisms responsible for osteoporosis and the modalities used to screen and diagnose this common disorder. Various therapeutic approaches now in use, and some promising experimental trials, will be discussed.

Calcitonin: physiological actions and clinical applications.

Calcitonin (CT) was first reported as a hypocalcemic principle, initially thought to originate from the parathyroid gland, a view subsequently corrected to an origin from parafollicular C-cells. Human CT is a 32 amino acid peptide with an N-terminal disulphide bridge and a C-terminal prolineamide residue, shown to potently inhibit bone resorption. More recent studies have demonstrated that this may take place through a direct osteoclastic action. A number of osteoclast CT receptors have subsequently been characterized and particular receptor regions necessary for ligand binding and intracellular signaling identified. Its potent anti-resorptive effect has led to its use in treating Paget's bone disease, osteoporosis, hypercalcaemia and osteogenesis imperfecta. This review summarises some key aspects of its synthesis, structure and its actions at the cellular and molecular levels, and leads on to its therapeutic uses that have emerged since its discovery as well as possibilities for future clinical applications.