‘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/m², 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 effects of transsphenoidal surgery on endocrine function and visual fields in patients with functionless pituitary tumours

Twenty-eight patients with functionless pituitary tumours have been treated by transsphenoidal surgery over the last 28 months. Mean age at presentation was 55 years. Tumor size was graded according to the extent of suprasellar extension on CT headscan from above the interclinoid line: four were small, 15 medium and nine large. Before surgery in 25 per cent of patients visual acuity and visual fields were normal. In the immediate postoperative period, 24 per cent of the patients with visual defects before surgery had normal vision, and in 38 per cent of the others it was improved. Six months after surgery, there had been further improvement; 43 per cent had normal vision and 48 per cent showed an overall improvement. In no patient did vision deteriorate following surgery. In the patients who presented with visual symptoms of one year or less, there was no correlation between the length of symptoms and the extent of visual recovery after surgery. Average age of the patients with full visual recovery was 47 +/- 4 years (mean +/- SEM); average age of the patients with only partial visual recovery was 63 +/- 3 years. Prolactin levels before surgery were elevated in 77 per cent of patients and fell significantly after operation, remaining elevated in 28 per cent of patients six months later. Fifty per cent of patients were treated with long-term hormone replacement therapy. Transsphenoidal surgery led to improved vision in the majority of patients, the results being comparable with those obtained with transfrontal surgery. Surgical complications were few, and long-term morbidity low. We suggest that the first-line treatment for patients with functionless pituitary tumours should be transsphenoidal surgery, even when large suprasellar extensions are present.