Bone Marrow Adiposity in Premenopausal Women With Type 2 Diabetes With Observations on Peri-Trabecular Adipocytes

Abstract

Context No study has evaluated the relationships among of bone marrow adiposity(BMA), bone histomorphometry(BH) and glycemic control in premenopausal women with type 2 diabetes(T2DM). Objectives Assess the effect of glycemic control on BMA;correlate the parameters of BH with BMA and correlate BMA with the use of hypoglycemic agents and with BMD. Design, settings and patients This was a cross-sectional study that evaluated 26 premenopausal women with T2DM were divided into groups with HbA1c<7% (GC,n=10) and HbA1c>7% (PC,n=16).BMA parameters (Ad.N, Ad.Pm, Ad.Ar, Ad.V/Ma.V and peri-trabecular adipocyte number (Ad.N/BS) were evaluated.BH static(BV/TV, O.Th, OS/BS) and dynamic parameters and serum IGF-1 were measured.BMA data were compared between the GC vs PC groups. Correlations were performed. Results Ad.N, Ad.Pm and Ad.Ar were higher in PC(all, p=0.04). HbA1c correlated positively with Ad.N/BS(p< 0.01) and Ad.N/BS correlated negatively with O.Th(p<0.01) and OS/BS(p=0.02). Positive and negative correlations were observed between insulin and metformin use, respectively, with all adipocyte parameters except Ad.N/BS(p<0.05). Structural parameters were negatively correlated with the BMA. BMD of the femoral neck(r = -549, p<0.01) and total femur(r=-0.502, p<0.01) were negatively correlated with Ad.V/Ma.V. Conclusion Poor glycemic control is associated with hyperplasia and hypertrophy of BMAs and with lower BVTV. Ad,N/BS, a new BMA parameter, is correlated with HbA1c and negatively with O.Th. The use of insulin seems to stimulate the expansion of BMA while that of metformin has the opposite effect. These findings suggest that the increase in BMA may play a role in the T2DM bone disease, on the other hand, good glycemic control might help prevent it.

Bone marrow adiposity in diabetes and clinical interventions

“…Lin et al followed 32 postmenopausal women with newly diagnosed T2D treated with metformin for 1 year, and reported that vertebral BMAT significantly decreased from 65.7% to 57.8% ( P <0.001) [20 ▪ ]. These findings are consistent with cross-sectional data that metformin use is associated with fewer and smaller BM adipocytes [25 ▪▪ ]. Whether these findings are due to direct effects of metformin or other factors such as improved glycemic control is not known.…”

“…Baum et al demonstrated that in women with T2D, those with HbA1c >7% had higher BMAT levels compared to those with HbA1c < 7% [21]. Similarly, multiple studies have demonstrated that BMAT is positively correlated with HbA1c although not fasting plasma glucose [19,21–24,25 ▪▪ ]. These findings suggest that BMAT may reflect longer-term glucose control.…”

“…Transiliac bone biopsy with tetracycline labeling was performed in 26 premenopausal women with T2D. Women with HbA1c >7% had BM adipocyte hyperplasia and hypertrophy with lower cancellous bone volume compared to women with HbA1c <7% [25 ▪▪ ]. The authors also identified a new BM adipocyte parameter that may reflect peri-trabecular adipocytes, which positively correlated with HbA1c and negatively with some bone formation parameters.…”

The extracellular matrix of human bone marrow adipocytes and glucose concentration differentially alter mineralization quality without impairing osteoblastogenesis

“…The bone marrow (BM) fat fraction negatively correlates with bone mineral density (BMD) in aging and menopause. It is also strongly associated with poor glycemic control in T2D ( Andrade et al, 2021 ; Yu et al, 2017 ), which is characterized by unchanged or even increased bone mass with compromised bone quality ( Schwartz, 2016 ). While BMAds can potentially affect both bone quantity and quality, their role has been primarily investigated in relation to bone remodeling.…”

A relação entre os tecidos adiposo e ósseo em indivíduos com lipodistrofia parcial familiar

“…No entanto, estes dados não são unânimes, uma vez que Zhu e colaboradores encontraram maior conteúdo de TAMO em pacientes com DM2 (Zhu et al, 2019). Além disso, em trabalho que avaliou a adiposidade de medula por meio de histomorfometria óssea via biópsia do ilíaco em mulheres jovens com DM2, foi observada correlação positiva do entre adipócitos de MO e HbA1c, e associação positiva entre mau controle glicêmico e hiperplasia e hipertrofia dos adipócitos do TAMO (Andrade et al, 2021).…”