Background Bone mineral density (BMD) of the femoral neck is used as part of the FRAX Tool to calculate a patient's 10 year probability of having a fragility fracture. Risk factors for a reduction in BMD include reduction in oestrogen in female patients. Amenorrhoea is a reliable clinical indicator of oestrogen deficiency as its occurrence coincides with a more rapid reduction in BMD (1). Patients with the onset of menopause before the age of 45 have previously been shown to be at risk of low BMD, but studies have not addressed whether a history of amenorrhoea was associated with a reduction in BMD.
Objectives To investigate whether secondary amenorrhoea causes a reduction in BMD compared to normal healthy controls after adjustment for possible confounders.
Methods Data of female individuals that underwent Dual-energy X-ray Absorptiometry scan at a District hospital in the North West of England between 1992 and 2010 were used. The age of patients was recorded as well as the BMD in femoral neck and lumbar spine. Other characteristics recorded included height and weight to calculate body mass index (BMI) and percentage body fat. Patients with secondary amenorrhoea or a history of amenorrhoea were compared to a female only control group with no identifiable risk factors for scanning. Initially, differences in age at scan, BMI and body fat were compared using a Student's T test. Logistic regression modelling, adjusted for age, BMI and body fat was used to examine any reduction in BMD of the lumbar spine or femoral neck between patients and controls.
Results 277 patients were identified that had secondary amenorrhoea or previous amenorrhoea. Median age was 44.2 years (IQR 34.9,50.75) compared to 4763 female controls median age 57.9 years (IQR 51.4,67.00). 53 (19.13%) of the patients had sustained a fracture. BMI in cases was significantly less than controls (23.4 kg/m2 vs 26.6 kg/m2 p<0.001). Body fat was also less in cases than controls (23.1% vs 29.1% p<0.001). The unadjusted odds ratio for a reduction of BMD of the lumbar spine was 0.36 (95% CI 0.18, 0.70) and in the femoral neck the odds were 3.52 (95% CI 1.19, 10.42). After adjusting for age, the odds ratio for a reduction in BMD of the lumbar spine was 0.05 (95% CI 0.02,0.11) and 0.08 (95% CI 0.01,0.33) for the femoral neck. Adjusting for age and BMI showed an OR of 0.09 (95%CI 0.04, 0.22) in the lumbar spine and OR 0.25 (95%CI 0.05,1.15) in the femoral neck. When adjusting for body fat and age at scan the odds were 0.15 (95%CI 0.05,0.46) in the lumbar spine and 0.13 (95%CI 0.03,0.56) in the femoral neck. Adjusting for both BMI and body fat gave odds of 0.21 (95%CI 0.07,0.68) and 0.21 (0.04,0.99) respectively.
Conclusions After adjusting for age and BMI, secondary amenorrhoea appears to have a detrimental effect on the BMD of the lumbar spine and a trend of effect on the femoral neck. When adjusting for percentage body fat it shows a reduction in both sites. As the FRAX tool uses femoral neck BMD and BMI as a predictor for fracture, not using percent body fat could lead to an underestimation of the fracture risk in this group of patients. Further research is required to investigate the effects of secondary amenorrhoea on BMD and its longitudinal prediction.
Choktanasiri W, Rojanasakul A, Rajatanavin R. Bone mineral density in primary and secondary amenorrhoea. J Med Assoc Thai. 2000 Mar;83 (3):243-8.
Disclosure of Interest None declared