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

J Clin Endocrinol Metab. 2021 Aug 18;106(9):e3592-e3602. doi: 10.1210/clinem/dgab322.

Abstract

Context: No study has yet evaluated the relationships among bone marrow adiposity (BMA), bone histomorphometry (BH), and glycemic control in premenopausal women with type 2 diabetes (T2DM).

Objective: We aimed to 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 bone mineral density (BMD).

Methods: This was a cross-sectional study that evaluated 26 premenopausal women with T2DM who were divided into groups with HbA1c < 7% (good control [GC], n = 10) and HbA1c > 7% (poor control [PC], n = 16). BMA parameters (adipocyte number [Ad.N], total adipocyte perimeter [Ad.Pm], total adipocyte area [Ad.Ar], percentage adipocyte volume per marrow volume [Ad.V/Ma.V]) and peri-trabecular adipocyte number divided by bone surface (Ad.N/BS) were evaluated. BH static (bone volume fraction [BV/TV], osteoid thickness [O.Th], osteoid surface/bone surface [OS/BS]) and dynamic parameters and serum insulin-like growth factor-1 were measured. BMA data were compared between the GC and 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 BV/TV. 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.

Keywords: bone disease; bone histomorphometry; bone marrow adipocytes; bone marrow adiposity; bone quality; type 2 diabetes mellitus; vertebral fractures.

Publication types

  • Observational Study

MeSH terms

  • Absorptiometry, Photon
  • Adipocytes / pathology*
  • Adiposity*
  • Adult
  • Bone Density / drug effects
  • Bone Marrow / metabolism*
  • Bone Marrow / pathology*
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Glycated Hemoglobin / analysis
  • Glycemic Control
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / therapeutic use
  • Insulin-Like Growth Factor I / analysis
  • Metformin / therapeutic use
  • Middle Aged
  • Premenopause / metabolism*
  • Trabecular Meshwork / metabolism*
  • Trabecular Meshwork / pathology*

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • IGF1 protein, human
  • Insulin
  • Insulin-Like Growth Factor I
  • Metformin