Effects of Diabetes on Bone Material Properties

Lekkala, Sashank; Taylor, Erik A.; Hunt, Heather B.; Donnelly, Eve

doi:10.1007/s11914-019-00538-6

Cited by 51 publications

(58 citation statements)

References 78 publications

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“…People with T2DM have normal or even higher bone mineral density compared with healthy people; 42 however, people with T2DM have a markedly higher risk for fracture 43,44 . Studies have demonstrated that bone strength is decreased in T2DM and that the bone microarchitecture is changed, especially affecting the cortical bone, leading to increased fragility 45 .…”

Section: Discussionmentioning

confidence: 99%

Progranulin promotes bone fracture healing via TNFR pathways in mice with type 2 diabetes mellitus

Ding

Wei

Hettinghouse

et al. 2021

Annals of the New York Academy of Sciences

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Type 2 diabetes mellitus (T2DM) significantly increases bone fragility and fracture risk. Progranulin (PGRN) promotes bone fracture healing in both physiological and type 1 diabetic conditions. The present study aimed to investigate the role of PGRN in T2DM bone fracture healing. MKR mice (with an FVB/N genetic background) were used as the T2DM model. Drill-hole and Bonnarens and Einhorn models were used to investigate the role of PGRN in T2DM fracture healing in vivo. Primary bone marrow cells were isolated for molecular and signaling studies, and reverse transcription-polymerase chain reaction, immunohistochemical staining, and western blotting were performed to assess PGRN effects in vitro. PGRN mRNA and protein expression were upregulated in the T2DM model. Local administration of recombinant PGRN effectively promoted T2DM bone fracture healing in vivo. Additionally, PGRN could induce anabolic metabolism during endochondral ossification through the TNFR2-Akt and Erk1/2 pathways. Furthermore, PGRN showed anti-inflammatory activity in the T2DM bone regeneration process. These findings suggest that local administration of exogenous PGRN may be an alternative strategy to support bone regeneration in patients with T2DM. Additionally, PGRN might hold therapeutic potential for other TNFR-related metabolic disorders.

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Section: Discussionmentioning

confidence: 99%

Progranulin promotes bone fracture healing via TNFR pathways in mice with type 2 diabetes mellitus

Ding

Wei

Hettinghouse

et al. 2021

Annals of the New York Academy of Sciences

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“…For example, overexpression of lysyl hydroxylases—which regulate the organization of enzymatic cross‐links in type 1 collagen—can change the molecular packing of collagen fibrils and lead to abnormal nucleation of hydroxyapatite crystals, ( 55 ) whereas inhibition of lysyl oxidase in rats decreased the concentration of mature collagen cross‐links by ~45% decreased femoral bending strength by 26% compared with controls. ( 58 ) Although the KKay mouse, ( 59 ) TallyHo mouse, ( 60 ) and ZDSD rat ( 61 ) similarly exhibit greater tissue mineral content (in contrast to mice fed a high‐fat diet ( 62 ) ), these models have limited ability to inform how progressive glycemic derangement alters tissue‐level and structural properties in bone because no rodent model captures (i) all of the observed changes in compositional properties, as reviewed recently ( 63 ) or (ii) the complexity of human T2DM (eg, longer duration, later onset). Together, the compositional differences identified here highlight several possible areas for future studies of the mechanisms of altered skeletal integrity with impaired glucose control and T2DM.…”

Section: Discussionmentioning

confidence: 99%

Bone Tissue Composition in Postmenopausal Women Varies With Glycemic Control From Normal Glucose Tolerance to Type 2 Diabetes Mellitus

Hunt

Miller

Hemmerling

et al. 2020

Journal of Bone and Mineral Research

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The risk of fragility fracture increases for people with type 2 diabetes mellitus (T2DM), even after controlling for bone mineral density, body mass index, visual impairment, and falls. We hypothesize that progressive glycemic derangement alters microscale bone tissue composition. We used Fourier‐transform infrared (FTIR) imaging to analyze the composition of iliac crest biopsies from cohorts of postmenopausal women characterized by oral glucose tolerance testing: normal glucose tolerance (NGT; n = 35, age = 65 ± 7 years, HbA1c = 5.8 ± 0.3%), impaired glucose tolerance (IGT; n = 26, age = 64 ± 5 years, HbA1c = 6.0 ± 0.4%), and overt T2DM on insulin (n = 25, age = 64 ± 6 years, HbA1c = 9.13 ± 0.6). The distributions of cortical bone mineral content had greater mean values (+7%) and were narrower (−10%) in T2DM versus NGT groups (p < 0.05). The distributions of acid phosphate, an indicator of new mineral, were narrower in cortical T2DM versus NGT and IGT groups (−14% and −14%, respectively) and in trabecular NGT and IGT versus T2DM groups (−11% and −10%, respectively) (all p < 0.05). The distributions of crystallinity were wider in cortical NGT versus T2DM groups (+16%) and in trabecular NGT versus T2DM groups (+14%) (all p < 0.05). Additionally, bone turnover was lower in T2DM versus NGT groups (P1NP: −25%, CTx: −30%, ucOC: −24%). Serum pentosidine was similar across groups. The FTIR compositional and biochemical marker values of the IGT group typically fell between the NGT and T2DM group values, although the differences were not always statistically significant. In summary, worsening glycemic control was associated with greater mineral content and narrower distributions of acid phosphate, an indicator of new mineral, which together are consistent with observations of lower turnover; however, wider distributions of mineral crystallinity were also observed. A more mineralized, less heterogeneous tissue may affect tissue‐level mechanical properties and in turn degrade macroscale skeletal integrity. In conclusion, these data are the first evidence of progressive alteration of bone tissue composition with worsening glycemic control in humans. © 2020 American Society for Bone and Mineral Research (ASBMR).

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“…Furthermore, it is important to consider that we have used standard material properties for the FE calculation, and it is possible that bone material properties could be altered in diabetes. (50,51) The risk of fractures is increased in T1D and despite the increased cortical porosity in T1DN+, the favorable trabecular findings in T1DN-might seem like a paradox. This paradox suggests a role for non-skeletal features on this increased risk.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Effects of Type 1 Diabetes and Diabetic Peripheral Neuropathy on the Musculoskeletal System: A Case–Control Study

Vilaça

Paggiosi

Walsh

et al. 2020

Journal of Bone and Mineral Research

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Fracture risk is increased in type 1 diabetes (T1D). Diabetic neuropathy might contribute to this increased risk directly through effects on bone turnover and indirectly through effects on balance, muscle strength, and gait. We compared patients with T1D with (T1DN+, n = 20) and without (T1DN−, n = 20) distal symmetric sensorimotor polyneuropathy and controls (n = 20). We assessed areal bone mineral density (aBMD) and appendicular muscle mass by dual‐energy X‐ray absorptiometry, microarchitecture by high‐resolution peripheral quantitative tomography at the standard ultra‐distal site and at an exploratory 14% bone length site at the tibia and radius, bone turnover markers, and muscle strength, gait, and balance by Short Physical Performance Battery (SPPB). At the standard ultra‐distal site, tibial cortical porosity was 56% higher in T1DN+ compared with T1DN− (p = .009) and correlated positively with the severity of neuropathy (Toronto Clinical Neuropathy Score; r = 0.347, p = .028) and negatively with nerve conduction amplitude and velocity (r = −0.386, p = .015 and r = −0.358, p = .025, respectively). Similar negative correlations were also observed at the radius (r = −0.484, p = .006 and r = −0.446, p = .012, respectively). At the exploratory 14% offset site (less distal), we found higher trabecular volumetric BMD (tibia 25%, p = .024; radius 46%, p = .017), trabecular bone volume (tibia 25%, p = .023; radius 46%, p = .017), and trabecular number (tibia 22%, p = .014; radius 30%, p = .010) in T1DN– compared with controls. Both CTX and PINP were lower in participants with TD1 compared with controls. No difference was found in aBMD and appendicular muscle mass. T1DN+ had worse performance in the SPPB compared with T1DN– and control. In summary, neuropathy was associated with cortical porosity and worse performance in physical tests. Our findings suggest that bone structure does not fully explain the rate of fractures in T1D. We conclude that the increase in the risk of fractures in T1D is multifactorial with both skeletal and non‐skeletal contributions. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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Effects of Diabetes on Bone Material Properties

Cited by 51 publications

References 78 publications

Progranulin promotes bone fracture healing via TNFR pathways in mice with type 2 diabetes mellitus

Progranulin promotes bone fracture healing via TNFR pathways in mice with type 2 diabetes mellitus

Bone Tissue Composition in Postmenopausal Women Varies With Glycemic Control From Normal Glucose Tolerance to Type 2 Diabetes Mellitus

The Effects of Type 1 Diabetes and Diabetic Peripheral Neuropathy on the Musculoskeletal System: A Case–Control Study

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