Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption.

Osteoclasts are large multinucleated bone-resorbing cells formed by the fusion of monocyte/macrophage-derived precursors that are thought to undergo apoptosis once resorption is complete. Here, by intravital imaging, we reveal that RANKL-stimulated osteoclasts have an alternative cell fate in which they fission into daughter cells called osteomorphs. Inhibiting RANKL blocked this cellular recycling and resulted in osteomorph accumulation. Single-cell RNA sequencing showed that osteomorphs are transcriptionally distinct from osteoclasts and macrophages and express a number of non-canonical osteoclast genes that are associated with structural and functional bone phenotypes when deleted in mice. Furthermore, genetic variation in human orthologs of osteomorph genes causes monogenic skeletal disorders and associates with bone mineral density, a polygenetic skeletal trait. Thus, osteoclasts recycle via osteomorphs, a cell type involved in the regulation of bone resorption that may be targeted for the treatment of skeletal diseases.

The management of low-risk primary upper gastrointestinal haemorrhage in the community: a 5-year observational study.

BACKGROUND: Acute upper gastrointestinal haemorrhage is a common medical emergency, initially managed with inpatient care. Bleeding stops spontaneously in over 80% of cases, indicating that patients with low-risk upper gastrointestinal haemorrhage may be more optimally managed in the community, without the need for admission to hospital. AIM: To assess the safety of managing patients with low-risk upper gastrointestinal haemorrhage without admission to hospital. METHODS: Prospective/retrospective study of all patients presenting to a UK teaching hospital with low-risk upper gastrointestinal haemorrhage who were managed without admission to hospital over 5 years. Low risk was defined as Glasgow Blatchford Score of 2 or less, age below 70 years, no other active medical problems, not taking warfarin and suspected nonvariceal bleed. Outcome measures were the need for intervention (blood transfusion, endoscopic therapy or surgery) and death. RESULTS: One hundred and forty-two patients fulfilled the inclusion criteria, and were managed without admission to hospital. No patients required endoscopic intervention, blood transfusion or surgery. The 28-day mortality was nil. Forty-one patients had normal endoscopic examination and 11 had significant endoscopic findings (peptic ulceration=10, oozing Mallory-Weiss tear=1) but did not require intervention. CONCLUSION: Patients presenting with a primary upper gastrointestinal haemorrhage aged below 70 years with a Glasgow Blatchford Score of 2 or less are at a low risk, and can be safely managed in the community.

Management of minor upper gastrointestinal haemorrhage in the community using the Glasgow Blatchford Score.

BACKGROUND: The Glasgow Blatchford Score (GBS) is a validated risk assessment tool in primary upper gastrointestinal haemorrhage, which accurately predicts the need for intervention (endoscopic therapy, blood transfusion or surgery) or death. AIMS: To identify the GBS that predicts lack of intervention or death and to apply this to clinical practice by managing low-risk patients in the community. METHODS: GBSs prospectively calculated on 232 patients with upper gastrointestinal haemorrhage to identify low-risk score. Patients with low-risk of requiring intervention (GBS