Bone Marrow Metabolism Is Impaired in Insulin Resistance and Improves After Exercise Training

Abstract

Context: Exercise training improves bone mineral density, but little is known about the effects of training on bone marrow (BM) metabolism. BM insulin sensitivity has been suggested to play an important role in bone health and whole-body insulin sensitivity.

Objective: To study the effects of exercise training on BM metabolism.

Design: Randomized controlled trial.

Setting: Clinical research center.

Participants: Sedentary healthy (n = 28, 40-55 years, all males) and insulin resistant (IR) subjects (n = 26, 43-55 years, males/females 16/10).

Intervention: Two weeks of sprint interval training or moderate-intensity continuous training.

Main outcome measures: We measured femoral, lumbar, and thoracic BM insulin-stimulated glucose uptake (GU) and fasting free fatty acid uptake (FFAU) using positron-emission tomography and bone turnover markers from plasma.

Results: At baseline, GU was highest in lumbar, followed by thoracic, and lowest in femoral BM (all Ps < 0.0001). FFAU was higher in lumbar and thoracic than femoral BM (both Ps < 0.0001). BM FFAU and femoral BM GU were higher in healthy compared to IR men and in females compared to males (all Ps < 0.05). Training increased femoral BM GU similarly in all groups and decreased lumbar BM FFAU in males (all Ps < 0.05). Osteocalcin and PINP were lower in IR than healthy men and correlated positively with femoral BM GU and glycemic status (all Ps < 0.05).

Conclusions: BM metabolism differs regarding anatomical location. Short-term training improves BM GU and FFAU in healthy and IR subjects. Bone turnover rate is decreased in insulin resistance and associates positively with BM metabolism and glycemic control.

Clinical trial registration number: NCT01344928.

Keywords: Bone marrow; PINP; exercise training; metabolism; osteocalcin; positron emission tomography.

© Endocrine Society 2020.

Figures

Figure 1.

(A) CONSORT flow diagram. The analyses were carried out using the intention-to-treat principle and included all the randomized participants. (B) Study design. Abbreviations: 18F-FDG, 2-[18F]fluoro-2-deoxy-D-glucose; 18F-FTHA, 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid; MICT, moderate-intensity continuous training; MRI, magnetic resonance imaging; OGTT, oral glucose tolerance test; SIT, sprint-interval training; VO2peak test, aerobic capacity;

Figure 1.

(A) CONSORT flow diagram. The analyses were carried out using the intention-to-treat principle and included all the randomized participants. (B) Study design. Abbreviations: 18F-FDG, 2-[18F]fluoro-2-deoxy-D-glucose; 18F-FTHA, 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid; MICT, moderate-intensity continuous training; MRI, magnetic resonance imaging; OGTT, oral glucose tolerance test; SIT, sprint-interval training; VO2peak test, aerobic capacity;

Figure 2.

An example of the shape and positioning of the region of interest (ROI) from which time activity curves were extracted. Sagittal PET/CT image of lumbar vertebral (A) and femoral (B) regions. Transaxial PET/CT image of lumbar vertebral (C) and femoral (D) regions. CT scans were used as anatomical reference.

Figure 3.

Substrate uptake differs according to anatomic region. Statistical analyses were done only between femoral, thoracic vertebral and lumbar vertebral bone marrow results. *P < 0.0001. Data are model-based means with 95% confidence intervals. Abbreviations: FFAU, free fatty acid uptake; GU, glucose uptake; IR, insulin resistant; QF, quadratus femoris muscle.

Figure 4.

(A-B) Bone marrow insulin-stimulated GU is impaired in IR group and improves after training. (C-D) Bone marrow fasting FFAU is higher in healthy subjects and IR women but improves after training in lumbar vertebrae. # difference at baseline, P < 0.05. *difference between pre- and post-measurements. P < 0.05. Data are model-based means with 95% confidence intervals. Abbreviations: FFAU, free fatty acid uptake; GU, glucose uptake; IR, insulin resistant; MICT, moderate-intensity continuous training; SIT, sprint-interval training.

Figure 5.

Baseline correlations. Healthy subjects have been marked with a circle and IR subjects with a square. Femoral bone marrow GU correlates positively with whole body insulin sensitivity, aerobic capacity, and negatively with BMI. There was no correlation between femoral bone marrow GU and FFAU. Abbreviations: BMI, body mass index; FFAU, free fatty acid uptake; GU, glucose uptake; IR, insulin resistant; M-value, whole-body insulin sensitivity; VO2peak, aerobic capacity. &Logarithmic transformation was performed to fulfill normal distribution assumption.

Figure 6.

Bone turnover marker correlations at baseline. Healthy subjects have been marked with a circle and IR subjects with a square. (A-B) Osteocalcin correlates positively with whole-body insulin sensitivity and femoral bone marrow GU. (C-D) Also PINP correlates positively with whole-body insulin sensitivity and femoral bone marrow GU. Abbreviations: GU, glucose uptake; IR, insulin resistant; M-value, whole-body insulin sensitivity; PINP, procollagen type 1 N-terminal propeptide. &Logarithmic transformation was performed to fulfill normal distribution assumption.