'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass.

SUMMARY: High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. INTRODUCTION: High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. METHODS: Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. RESULTS: Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m(2), p < 0.001). CONCLUSION: Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass.

The prevalence and management of hyperglycaemia in patients with rheumatoid arthritis on corticosteroid therapy.

BACKGROUND AND AIMS: Corticosteroids are commonly used in the treatment of RA. Hyperglycaemia resulting from corticosteroid use can lead to problems, particularly in those with impaired glucose tolerance and diabetes mellitus. We have examined how rheumatology clinics monitored and managed hyperglycaemia at base line and during treatment of patients with rheumatoid arthritis on corticosteroids. METHODS: Case notes of 102 patients with established RA, on long-term steroids were reviewed. We recorded a) blood glucose level at base line and whilst on steroids b) when and whether hyperglycaemia was addressed. RESULTS: There were 24 males and 78 females, with mean age of 62 +/- 15 years. Patients were on corticosteroids for a median duration of 24 months. Seventy-five per cent of patients were treated with oral prednisolone, the rest, except one patient on deflazacort, were on methylprednisolone. Blood glucose was measured at baseline in 97% of patients with 37% and 38% being monitored at three months and six months respectively and 36% annually thereafter. Nine patients (8.8%) developed diabetes mellitus during treatment, but one patient was detected and managed. There were six patients with existing diabetes mellitus in whom glycaemic control worsened between three to six months, but only one patient had treatment adjusted. CONCLUSIONS AND RECOMMENDATIONS: Physicians need to be aware that corticosteroids can increase blood glucose, worsen pre-existing diabetes and predispose to diabetes mellitus. Patients on long-term corticosteroids should be monitored at regular intervals as corticosteroid induced glycaemic excursions may lead to the development of diabetes mellitus and increased coronary risk.