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Cited by 260Bone health and osteoporosis researchBone Metabolism and DiseasesHIV-related health complications and treatments

Update on the pathogenesis and treatment of skeletal fragility in type 2 diabetes mellitus

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Khosla, Sundeep, Samakkarnthai, Parinya, Monroe, David G., Farr, Joshua N.·2021·Nature Reviews Endocrinology
DOI 10.1038/s41574-021-00555-5PMC PMC8605611
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Abstract

Fracture risk is increased in patients with type 2 diabetes mellitus (T2DM). In addition, these patients sustain fractures despite having higher levels of areal bone mineral density, as measured by dual-energy X-ray absorptiometry, than individuals without T2DM. Thus, additional factors such as alterations in bone quality could have important roles in mediating skeletal fragility in patients with T2DM. Although the pathogenesis of increased fracture risk in T2DM is multifactorial, impairments in bone material properties and increases in cortical porosity have emerged as two key skeletal abnormalities that contribute to skeletal fragility in patients with T2DM. In addition, indices of bone formation are uniformly reduced in patients with T2DM, with evidence from mouse studies published over the past few years linking this abnormality to accelerated skeletal ageing, specifically cellular senescence. In this Review, we highlight the latest advances in our understanding of the mechanisms of skeletal fragility in patients with T2DM and suggest potential novel therapeutic approaches to address this problem.

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  • Diabetes mellitus is strongly associated with osteoporosis.

    “There are strong associations between diabetes mellitus and numerous concurrent health issues, such as osteoporosis, thyroid dysfunction, and abnormalities in iron metabolism (2–4).”

    From Biological variation in serum thyroid, iron metabolism, and plasma bone metabolism biomarkers in patients with type 2 diabetes mellitus (2025) · cites this paper as [3]

    The Treatment of skeletal fragility in T2DM section explicitly discusses osteoporosis in patients with type 2 diabetes, and the paper reports increased fracture risk in that group. The citing sentence refers to diabetes mellitus generally, whereas this source addresses type 2 diabetes specifically. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Diabetes mellitus is strongly associated with thyroid dysfunction.

    “There are strong associations between diabetes mellitus and numerous concurrent health issues, such as osteoporosis, thyroid dysfunction, and abnormalities in iron metabolism (2–4).”

    From Biological variation in serum thyroid, iron metabolism, and plasma bone metabolism biomarkers in patients with type 2 diabetes mellitus (2025) · cites this paper as [3]

    The Abstract discusses increased fracture risk and skeletal fragility in type 2 diabetes, but does not address thyroid dysfunction. Searches for thyroid dysfunction, hypothyroidism and hyperthyroidism found no passage in our copy supporting the claimed association. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

  • Diabetes mellitus is strongly associated with abnormalities in iron metabolism.

    “There are strong associations between diabetes mellitus and numerous concurrent health issues, such as osteoporosis, thyroid dysfunction, and abnormalities in iron metabolism (2–4).”

    From Biological variation in serum thyroid, iron metabolism, and plasma bone metabolism biomarkers in patients with type 2 diabetes mellitus (2025) · cites this paper as [3]

    The Pathogenesis of skeletal fragility in T2DM section discusses bone quality and diabetic complications, but not iron metabolism. Searches of the indexed copy for iron metabolism, ferritin, and hepcidin found no passage addressing the claimed association. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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References 166 · Cited by 260

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Authors
Khosla, S., Samakkarnthai, P., Monroe, D. G., & Farr, J. N.
Affiliations
Mayo Clinic (US)
Corresponding author
Khosla, Sundeep
ORCID
Venue
Nature Reviews Endocrinology
Publisher
Springer Science and Business Media LLC
Published
2021-09-13
Volume
17
Issue
11
Pages
685-697
ISSN
  • 1759-5029 (ISSN-L)
  • 1759-5037
DOI
10.1038/s41574-021-00555-5
PMC
PMC8605611
OpenAlex
W3200776176
Cited by
260
References
166
Citations by year
2026: 65 · 2025: 66 · 2024: 71 · 2023: 34 · 2022: 22 · 2021: 1 · 2020: 1
FWCI
6.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Reviews Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (R56AG063707, R01AG063707, P01AG004875, R21AG065868, P01AG062413)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK128552)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR068275, K01AR070241, R01AR027065)
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
Keywords
type 2 diabetes, bone fragility, fracture risk, bone quality, bone material properties, cortical porosity, bone formation, cellular senescence, diabetes complications
MeSH terms
Animals, Bone and Bones, Diabetes Mellitus, Type 2, Humans, Absorptiometry, Photon, Bone Density, Fractures, Bone

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