Interestingly, HBM cases had a lower mean platelet count than controls; although the difference was relatively small and could have arisen by chance, it is interesting to note that platelet dysfunction has been linked to raised bone mass through the RANKL/OPG pathway in Ghosal syndrome [30] and B-integrins in mice models [31] and one

infant [32]. Finally, HBM cases had a greater BMI, which as far as we are aware has not previously been reported in this context [12, 15]. The proportions of this BMI difference explained by fat, lean and bone mineral mass remain to be QNZ determined. Gains in fat mass may reduce validity of DXA measures [33, 34], with obesity potentially leading to misclassification of HBM status. If BMD was overestimated find more in individuals with greater fat mass, the latter may have been over-represented in the recruited

population, explaining the observed BMI association. In terms of study weaknesses, our use of relatives to provide both cases and controls to analyses examining clinical characteristics Dasatinib cost is likely to have underestimated differences (than had cases been compared with general population controls), due to shared genetic factors, particularly as we had to apply an arbitrary Z-score threshold to a continuous BMD distribution to assign case and control status. However, the fact that albeit partially attenuated differences were seen in further analyses, comparing index cases to relatives and spouses combined, suggests that the precise threshold used to separate relatives into cases and controls had little impact on the overall findings. Our HBM definition threshold will still have included some individuals with co-morbid lumbar OA. Our analysis strategy, clustering by family, endeavours to take account MycoClean Mycoplasma Removal Kit of over-representation of features common within larger families. Our study design most likely accounts for differences observed between cases and controls in terms of age, gender, post-menopausal status and oestrogen treatment use, given

the gender and age biases inherent in those referred to NHS DXA services. For example, index cases were more often female and their relationships heterosexual, so partner controls were more often male. That more female relatives were recruited may be explained by differential employment restrictions on clinic attendance or greater awareness of bone disease issues such, as osteoporosis, amongst women. As index cases were more often post-menopausal, their children rather than their parents were more likely to participate, explaining the age difference between cases and controls. Overall, low response rates reduce generalisability and increase the possibility of non-response bias. Large epidemiological studies report response rates of approximately 60% [35, 36].