The present study looks at the BMD differences in T1DM and age, sex, and BMI matched controls. It also tries to find out the possible factors associated with poor BMD in T1DM population. Though many studies have focused on BMD in T1DM, very few have looked at the possible determinants of poor BMD in the population. To the best of our knowledge, this is the first study in the Indian population trying to deal with BMD and its determinants in T1DM.
The study clearly demonstrates that BMD in T1DM is low as compared to age, sex, and BMI matched controls. Previous studies regarding BMD in T1DM have been inconsistent. 3 major meta-analyses dealing with bone health in T1DM and the reports of various studies included in these meta-analyses are very variable. Vestergaard and Strotmeyer found that BMD was lower at hip and spine in T1DM and the later also found that older age and longer duration of T1DM were associated with poorer BMD [1
]. Vestergaard and Janghorbani found an increased risk of hip fracture in T1DM [1
]. No conclusive relation of glycaemic control to BMD was found in the above studies. A consistent finding observed in these studies and the 3 major meta-analyses is the increased risk of fractures [1
Various factors have been studied, individually or in combination, by various authorities for their impact on BMD in T1DM. Factors claimed to be variably associated with poor BMD are younger age of onset of diabetes [3
], female sex [1
], longer duration of diabetes [3
], poor glycaemic control, lower height, lower BMI, vitamin D deficiency, increased bone resorption markers, decreased bone formation, associated complications of diabetes, and associated celiac disease (CD) [1
Few studies suggested increased bone resorption while others proposed loss of bone formation as the cause of low BMD in T1DM [6
]. In our study, we did not test for any selective resorptive/absorptive marker except alkaline phosphatase which correlated negatively with total body BMD, but the difference is mainly due to the difference in the male population.
Reports have been variable about sex differences in bone health in T1DM. In our study, the difference in total body BMD was mainly due to the difference in female population who also had a greater deficit in BMC as compared to controls which is similar to the observations by Leger et al. In another study by Saha et al. dealing with bone mass and structure, diabetic boys seemed to be more affected than diabetic girls [6
]. Among the boys, the mean deficit in BMC of all measured skeletal sites was more than 10%, while among the girls it was less than 5% [7
Younger age of onset of diabetes has been associated with poor BMD which continues to persist over years as noted in few studies as the one by Mastrandrea et al. [8
]. In our study, the younger age of onset was associated with poor total body BMD (P
= 0.03), but the value did not achieve significance at lumbar spine BMD (P
= 0.09). However, we think that the value would have reached significance with more number of patients included in the study.
Anthropometry and body composition did not correlate with BMD except that females with higher fat percentage had better BMD. Higher body fat percentage has been associated with better BMD by many few studies previously, and factors like adipocytokines and increased estrogen levels have been proposed as possible reasons [8
Better glycaemic control, a proven measure to decrease/avoid end-organ damage, also was associated with better bone health [9
]. Lower HbA1c was associated with better BMD. Also poor BMD was associated with lower IGF-1 levels which again is a result of poor glycaemic control [11
]. Poor glycaemic control may worsen BMD and increase the fracture risk by increasing calcium excretion in urine, accumulation of advanced glycation products, inducing a proinflammatory state, causing lower IGF-1 levels (which has bone anabolic action), and lowering pH/acidosis [1
IGFs increase bone matrix synthesis and bone formation. Both the systemic circulating as well as the locally synthesized IGF-I contribute to bone formation. IGF-I increases osteoclastogenesis and bone remodeling. Both IGF-I and IGF-II are synthesized by bone cells and stored in the bone matrix, but IGF-1 is a more potent stimulator of osteoblastic function. PTH and PGE2 are major inducers of skeletal IGF-1 synthesis, and glucocorticoids suppress IGF-1 transcription. IGFs mediate selected effects of these hormones on bone formation [11
A previous independent study by Campos et al. reported that poor glycaemic control is associated with poor BMD, and the later also reported improvement in BMD with improved glycaemic control. However, quite a few studies done previously found no relation between BMD and glycaemic control [9
That better physical activity is associated with better BMD; a known and time-tested fact was reemphasized in our study. A recent study by Nihlsson et al. suggests that increased physical activity is associated with the enhanced development of peak bone mass [13
Previous studies have also looked at the prevalence of various complications and the relation with BMD. Some concluded that lower BMD was associated with the presence of retinopathy or nephropathy, while others did not [1
]. An independent study by Eskildsen found poor BMD in T1DM with neuropathy [14
]. In our study, we did not find any difference in BMD associated with any particular complication.
Most studies reported lower BMD in CA+ T1DM except the one by Simmons et al., where the results may be biased due to the healthy volunteer effect [15
]. The additive BMD lowering effect of CD may be due to the underlying inflammatory state increasing bone resorption, malabsorption and increased nutritional deficiencies, associated hypogonadism, and GH resistance [16
]. The lower BMI in CD may add to increased fracture risk in these patients [16
The important limitations of the study are that bone turnover markers were not assayed. The objective evidence of neuropathy by doing nerve conduction velocity was not obtained, so a number of patients with peripheral neuropathy could have been underestimated. The HbA1c values of the last one year were used, so effects due to poor glycaemic control in past years could have been discounted.
To conclude, poor BMD in T1DM is associated with CA, lower physical activity, poor glycaemic control, lower IGF-1 levels, higher alkaline phosphatase levels (males), and lower total body fat (females) which may translate into a higher fracture risk. Improved glycaemic control and regular physical activity may result in a better bone health apart from the other known benefits in T1DM.