The bone remodelling cycle.

The bone remodelling cycle replaces old and damaged bone and is a highly regulated, lifelong process essential for preserving bone integrity and maintaining mineral homeostasis. During the bone remodelling cycle, osteoclastic resorption is tightly coupled to osteoblastic bone formation. The remodelling cycle occurs within the basic multicellular unit and comprises five co-ordinated steps; activation, resorption, reversal, formation and termination. These steps occur simultaneously but asynchronously at multiple different locations within the skeleton. Study of rare human bone disease and animal models have helped to elucidate the cellular and molecular mechanisms that regulate the bone remodelling cycle. The key signalling pathways controlling osteoclastic bone resorption and osteoblastic bone formation are receptor activator of nuclear factor-κB (RANK)/RANK ligand/osteoprotegerin and canonical Wnt signalling. Cytokines, growth factors and prostaglandins act as paracrine regulators of the cycle, whereas endocrine regulators include parathyroid hormone, vitamin D, calcitonin, growth hormone, glucocorticoids, sex hormones, and thyroid hormone. Disruption of the bone remodelling cycle and any resulting imbalance between bone resorption and formation leads to metabolic bone disease, most commonly osteoporosis. The advances in understanding the cellular and molecular mechanisms underlying bone remodelling have also provided targets for pharmacological interventions which include antiresorptive and anabolic therapies. This review will describe the remodelling process and its regulation, discuss osteoporosis and summarize the commonest pharmacological interventions used in its management.

Streptococcus equi subspecies zooepidemicus meningitis--a case report and review of the literature.

A case is described of a 79-year-old man, trampled by his horses, who subsequently developed a wound infection and, later, meningitis. Streptococcus equi subsp. zooepidemicus was isolated as the causative organism. S. equi subsp. zooepidemicus, which carries the Lancefield Group C antigen, is an uncommon human pathogen but is commonly isolated from bacterial infections in animals, particularly horses. It is most commonly acquired by humans following animal contact. A review of the literature identified 20 previously described cases of S. equi subsp. zooepidemicus meningitis. Crude mortality following infection was 24%. All of the patients who died were over 70 years of age and the ingestion of unpasteurised dairy products was associated with all but one of the fatal cases. Hearing loss was a frequent complication, occurring in 19% of cases. Only 38% of patients made a complete recovery. Treatment regimes commonly included benzylpenicillin or a third-generation cephalosporin, with a mean treatment duration in survivors of 23 days.

Extremely rapid recovery of human cone circulating current at the extinction of bleaching exposures.

We used a conductive fibre electrode placed in the lower conjunctival sac to record the a-wave of the human photopic electroretinogram elicited by bright white flashes, delivered during, or at different times after, exposure of the eye to bright white illumination that bleached a large fraction (approximately 90%) of the cone photopigment. During steady-state exposures of this intensity, the amplitude of the bright-flash response declined to approximately 50% of its dark-adapted level. After the intense background was turned off, the amplitude of the bright-flash response recovered substantially, for flashes presented within 20 ms of background extinction, and fully, for flashes presented 100 ms after extinction. In addition, a prominent 'background-off a-wave' was observed, beginning within 5-10 ms of background extinction. We interpret these results to show, firstly, that human cones are able to preserve around half of their circulating current during steady-state illumination that bleaches 90% of their pigment and, secondly, that following extinction of such illumination, the cone circulating current is restored within a few tens of milliseconds. This behaviour is in stark contrast to that in human rods, where the circulating current is obliterated by a background that bleaches only a few percent of the pigment, and where full recovery following a large bleach takes at least 20 min, some 50,000 times more slowly than shown here for human cones.