Osteoporosis: therapeutic update

G Russell

The Botnar Research Centre, Oxford University Institute of Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Headington, Oxford, UK

Summer School 13-16 July 2004
St Anne's College, Oxford University, UK

Osteoporosis is the commonest disorder of bone. The commonly quoted figures state that one in three women will have a fracture over the age of 50, and one in twelve men. The changes that occur in osteoporosis can be understood in terms of subtle but important disturbances in bone remodelling. Bone is metabolically active throughout life. After skeletal growth is complete, remodelling of both cortical and trabecular bone continues and requires the co-ordinated actions of osteoclasts to remove bone, and osteoblasts to replace it.

Drugs that will benefit osteoporosis can achieve this in three possible ways, by inhibiting bone resorption, by stimulating bone formation, or a combination of both. Up until recently, all the major drugs used to prevent or treat osteoporosis are inhibitors of bone resorption, and thereby of remodelling. This includes oestrogens and oestrogen-related compounds, particularly the SERMs (Selective Estrogen Receptor Modulators, the first of which is raloxifene), and bisphosphonates and calcitonin. The best evidence for reduction in fractures exists for bisphosphonates, particularly alendronate and risedronate, and for raloxifene.

With all the anti-resorptive drugs the degree of reduction of fracture rates that can be achieved in osteoporosis appear to be greater than might be predicted from the usually quite modest increases that occur in BMD. Factors that contribute to fracture reduction probably include preservation of microarchitecture, and increased mineralisation of individual osteons whose renewal rate is reduced when bone turnover slows down as a result of drug treatment. Desirable objectives of therapy must be to reduce bone resorption to a level where anti-fracture efficacy is optimal without impairing the quality of treated bone in the long term.

The potency of individual BPs both in experimental systems and in clinical usage is strongly correlated to their specific biochemical effects within osteoclasts. There is much current interest in assessing the value of different dosage regimens for bisphosphonates, ranging from daily oral administration through to once-yearly parenteral administration. The introduction of once-weekly formulations has enhanced the ease of administration and acceptability to patients. Potential differences between BPs has raised important questions not only about their relative potency but also the speed of ‘on’ and ‘off’ effects and duration of action. The retention time of individual BPs in bone may contribute to the persistence of action as well as to potency. Recent studies reveal potentially important differences in mineral binding affinities among the BPs that may be responsible for these effects.

In the future, there will be an increasing emphasis on the development of drugs that stimulate bone formation, as so-called anabolic agents. It would obviously be a significant advance if such anabolic agents could be developed that would enhance the formation of new bone and therefore produce bigger changes in bone mass and strength than can be achieved with current anti-resorptive drugs. The impressive clinical results recently obtained with teriparatide (recombinant human 1-34 sequence of parathyroid hormone) are a forerunner of other opportunities in this area. Strontium is another new drug on the horizon, which reduces fractures by the apparent dual action of reducing resorption and increasing formation.

We are moving rapidly from an era when only few drugs were available to one where more and better methods of treatment are likely to exist. Although we can predict what is likely to happen over the next few years, beyond that it is probable that the approaches to osteoporosis and its management will evolve substantially from what we do now.

The challenges in the future will include the problem of translating the increase in knowledge in the basic sciences to the benefit of as many patients as possible in an efficient and cost-effective manner. The increasing emphasis on evidence-based medicine and the political needs to limit costs of health care will play a large part in what can be achieved.

The opinions expressed in this paper are those of the speaker and do not necessarily reflect the views of the Society

Revised: 05-Nov-2004