Endocrine Abstracts

Parathyroid hormone in the treatment of osteoporosis: The Dawn of the anabolic era

G Russell

The Botnar Research Centre and Oxford University Institute of Musculoskeletal Sciences, Nuffield Department of Orthopaedic Surgery, Nuffield Orthopaedic Centre, Headington, Oxford, OX3 7LD, UK

All of the new drugs that have been used or become available over the past decade for the prevention and treatment of osteoporosis are so-called “anti-resorptives”. These include bisphosphonates (etidronate, alendronate and risedronate), hormone replacement therapy, selective estrogen receptor modulators (raloxifene), and calcitonins. All reduce vertebral fracture risk and some reduce nonvertebral fracture risk, but there are obvious theoretical advantages to using agents that stimulate bone formation and restore lost bone architecture. Parathyroid hormone (PTH) is the first of such anabolic agents to be approved for treatment of osteoporosis.

PTH given by once daily injections stimulates bone formation on trabecular and cortical bone surfaces by increasing the number and activity of osteoblasts. In contrast, continuous excess of endogenous PTH, as occurs in hyperparathyroidism, can lead to bone loss through increased bone resorption. Teriparatide is the name given to the biologically active N-terminal 34 amino acid portion of PTH. In a recent large trial (1637 patients) with recombinant human teriparatide, patients treated with 20 and 40 μg/day had increases in lumbar spine BMD of 9.7% and 13.7% respectively. There was a 65% reduction in vertebral fractures (even greater in patients with existing fractures) and a 55% reduction in non-vertebral fractures (Neer et al. N Engl J Med 2001 344 1434-1441). These effects are at least comparable to, and probably better than, those achieved with any of the anti-resorptive treatments. PTH therefore offers an exciting prospect of being able to reverse some of the skeletal changes of osteoporosis. Research continues into understanding the cellular basis for these effects. Practical issues with regard to its clinical use include how to select patients for treatment, its use in men, the impact of prior and subsequent treatment with other drugs, particularly long-acting bisphosphonates, and the duration of responses beyond the currently recommended treatment period of 18 months.

Endocrine Abstracts (2003) 6 S21