Commentary: The Five Ws of a Fracture Liaison Service: Why, Who, What, Where, and How? In Osteoporosis, We Reap What We Sow

Establishing a Fracture Liaison Service (FLS) to identify and treat patients with a recent fragility fracture has been shown to be effective, save money, useful to document high quality of care, and makes good clinical sense. A FLS starts with an osteoporosis champion and encompasses identification of patients with a recent fracture, diagnostic workup, treatment, and follow-up. A FLS is most effective when it is able to function in multiple settings: the hospital, emergency department, and outpatient clinic. Implementation may be somewhat easier in a closed healthcare system but can be feasible even in an open system. There are many barriers to implementation which can be addressed. The future of FLS care lies in a collaborative systems-based approach with appropriate stakeholder engagement, leading to seamless integration of osteoporosis care.     

Practical Experience of the Application of a Weighted Burden Test to Whole Exome Sequence Data for Obesity and Schizophrenia

For biological and statistical reasons it makes sense to combine information from variants at the level of the gene. One may wish to give more weight to variants which are rare and those that are more likely to affect function. A combined weighting scheme, implemented in the SCOREASSOC program, was applied to whole exome sequence data for 1392 subjects with schizophrenia and 982 with obesity from the UK10K project. Results conformed fairly well with null hypothesis expectations and no individual gene was strongly implicated. However, a number of the higher ranked genes appear plausible candidates as being involved in one or other phenotype and may warrant further investigation. These include MC4R, NLGN2, CRP, DONSON, GTF3A, IL36B, ADCYAP1R1, ARSA, DLG1, SIK2, SLAIN1, UBE2Q2, ZNF507, CRHR1, MUSK, NSF, SNORD115, GDF3 and HIBADH. Some individual variants in these genes have different frequencies between cohorts and could be genotyped in additional subjects. For other genes, there is a general excess of variants at many different sites so attempts at replication would be more difficult. Overall, the weighted burden test provides a convenient method for using sequence data to highlight genes of interest.