Serine proteases in bone disease

Serine proteases are active in many physiological and pathological processes within bone tissue. Although essential to adequate maintenance of bone and cartilage, their inappropriate expression can lead to exacerbation of tissue destruction and inflammation. Their effects are exerted through multiple pathways, including interaction with signalling molecules such as transforming growth factor ß (TGFß), binding to protease-activated receptors (PARs), and direct proteolysis of extracellular matrix proteins, in some cases working synergistically with matrix metalloproteases in the remodelling of bone tissue. The overall effect of these interactions is not yet clear, but there are strong links between some serine proteases and arthropathies, in addition to metastatic bone invasion. Understanding the contribution of each of these enzymes to the molecular disease process is crucial to developing effective treatment based on inhibitors or agonists. Serine protease inhibitors have shown promise in reducing the severity of arthritis, but greater specificity is required to avoid undesired systemic effects. © 2009 Bentham Science Publishers Ltd.

Multicentre trial of weekly risedronate on bone density in adults with cystic fibrosis

Background: The aim of this study was to assess the efficacy, tolerability and safety of risedronate in adults with CF. Methods: Patients with a lumbar spine (LS), total hip (TH) or femoral neck (FN) bone mineral density (BMD) Z-score of -1 or less were randomised to receive risedronate 35mg weekly or placebo, and calcium (1g)+vitamin D (800IU). Results: At baseline, BMD Z-scores in the risedronate (n = 17) and placebo (n = 19) groups were similar. By 24. months, 7/17 risedronate patients vs 0/19 placebo patients stopped the study medication due to bone pain. After 24. months treatment, the mean difference (95% CI) in change in LS, TH and FN BMD between the risedronate vs placebo groups was 4.3% (0.4, 8.2) p = 0.03; 4.0% (-0.5, 8.6) p = 0.08; and 2.4% (-3.5, 8.2) p =0.41. Conclusions: After two years treatment there was a significant increase in LS BMD with weekly risedronate compared to placebo. © 2011 European Cystic Fibrosis Society.

Late onset immune pancytopenia following bone marrow transplantation

A 17-year-old boy developed autoimmune pancytopenia in the absence of chronic graft-versus-host disease 170 d after allogeneic bone marrow transplantation (BMT) from his HLA identical brother. The anaemia and thrombocytopenia responded to conventional immunosuppressive treatment, but the neutropenia was refractory to this and to splenectomy and subsequent removal of splenic remnant. Following total lymphoid irradiation the neutrophil count rose to low normal levels but thrombocytopenia and anaemia secondary to marrow hypoplasia required transfusion support. Bone marrow function was finally normalized by an additional transfusion of donor marrow without prior immunosuppressive therapy. We conclude that late onset immune pancytopenia post BMT caused by antibodies of probable donor origin may be life threatening in the absence of chronic graft-versus-host disease.